Speaker

Martin Kiwanuka & Avery Rui Sun

echanobiology Institute, National University Singapore, Singapore

Topics

A MICROFLUIDIC STIFFNESS GRADIENT HYDROGEL PLATFORM FOR PROBING THE ROLE OF MATRIX STIFFNESS IN CANCER CELL INVASION

Cancer cell behavior has been shown to depend on the stiffness of the microenvironment, which is elevated in tumors vs. healthy tissue. Most studies examining the role of tumor stiffness in cancer progression use materials of defined stiffness; however, the stiffness of the tumor microenvironment is heterogeneous. To address this, we developed a stiffness gradient hydrogel system ranging from E ~ 0.5-18 kPa in a microfluidic device mimicking healthy to breast tumor stiffness. The stiffness gradient was created by photo-crosslinking gelatin methacrylate (GelMA) with a gradient transparency photomask. The fabricated system was then used for screening metastatic (MDA-MB-231) and non-metastatic (MCF-7) breast cancer cell invasion in a 3D environment by separately seeding cells into the top channel of the device and culturing with or without chemoattractant (epidermal growth factor, EGF) added to the bottom channel of the device. After 5 days, samples were fixed and immunostained to analyze invasion, cellular morphology, mechanotransduction, and proliferation as a function of stiffness. Our results show that the invasion of the metastatic breast cancer cells increased with stiffness, and while EGF enhanced the rate of invasion, the invasion pattern was dictated by stiffness. Cell volume and shape were linearly correlated with stiffness, with larger, more spread cells observed in stiffer regimes. In contrast, non-metastatic breast cancer cells did not invade the hydrogels, likely due to a downregulation in MMPs and/or contractility. In the future, the developed stiffness gradient system can aid in the discovery of novel therapeutic strategies to combat cancer cell invasion.

HYBRID SCAFFOLDS ELUCIDATE DISTINCT ROLES OF EXTRACELLULAR MATRIX IN AGE-RELATED CARDIAC FIBROBLAST ACTIVATION

Extracellular matrix (ECM) remodeling of cardiac tissue is a key contributor to age-related cardiovascular disease and dysfunction. In aging, many ECM components have been shown to undergo aberrant secretion, structural alterations, and/or degradation. Importantly, heart tissue stiffens with age, which can directly lead to compromised organ physiology and cell behavior. However, these changes in ECM are a multifaceted phenomenon due to the fact that compositional alterations, which trigger biochemical signaling in cells, are often accompanied by stiffness changes, which alter mechanosensitive signaling. To identify the specific roles of these interconnected ECM cues in cellular function, we describe a decellularized ECM-synthetic hydrogel hybrid scaffold that maintains native matrix composition and organization of young or aged murine cardiac tissue with independently tunable scaffold mechanical properties that mimic young (~10 kPa) or aged (~40 kPa) cardiac stiffness. Using quantitative assays, immunohistochemistry, and nanoindentation, we confirmed the preservation of native ECM (collagen, fibronectin, laminin, GAG) and independently tunable stiffnesses. Re-seeding these scaffolds with primary cardiac fibroblasts (CFs) from young or aged murine hearts followed by immunofluorescence examining (a-smooth muscle actin, paxillin, yes-associated protein 1) and RNA-seq, we identify distinct age-dependent mechanisms of CF activation in which CFs integrate both biochemical cues and mechanical cues to determine their phenotypical transition toward myofibroblasts, while young ECM biochemistry can notably outweigh the profibrotic stiffness cues in maintaining CF quiescence. Ultimately, these tunable scaffolds allow for the precise investigation into the role of specific ECM properties in regulating aging dysfunction and rejuvenation.

On site:

Seminarraum - Raum 314

Institute of Molecular and Cellular Anatomy (MOCA)

Wendlingweg 2, 52074 Aachen

Host:

Jacopo Di Russo

Interdisciplinary Centre for Clinical Research (IZKF)

Contact:

me3t@ukaachen.de

Speaker:

Prof. Wolfgang Wall, LMU München

On site:

Seminarraum „Alte Werkstatt“

MTI-2 Gebäude, Wendlingweg 2

Erdgeschoss, Raum 38

Organizers:

Prof. Stefan Uhlig

Institut für Pharmakologie und Toxikologie

Speaker

David J. Beech

Leeds Institute of Cardiovascular and Metabolic Medicine

School of Medicine, University of Leeds

https://medicinehealth.leeds.ac.uk/medicine/staff/1121/professor-david-j-beech

Topics

The two PIEZOs, PIEZO1 and PIEZO2, were first reported in 2010. These proteins form trimeric ion channels with little resemblance to other ion channels. A striking feature is their exquisite, robust and apparently specific sensitivity to activation by a range of mechanical forces. There is widespread agreement that they are bona fide direct sensors of force. We identified the importance in cardiovascular biology, first showing PIEZO1’s activation by physiological force and its roles in embryonic vascular maturation and the sensing of fluid shear stress as generated by blood flow. This and subsequent work firmly established PIEZO1’s role in endothelial biology and showed its ability to integrate force with vascular architecture. By generating conditional genetic deletion in the adult mouse to avoid embryonic lethality we found that endothelial PIEZO1 is required for elevated blood pressure of whole body physical activity, necessary for capillary density in skeletal muscle and critical in physical exercise performance. Such functions require continuous activity of PIEZO1 and so it was perplexing how this could be possible when over-expression studies reveal powerful intrinsic inactivation gates in PIEZOs. However, we showed that native PIEZO1 channels of endothelial cells are non-inactivating. We discovered the mechanism by which the inactivation gate is disabled, unexpectedly through relationship of PIEZO1 to sphingomyelinase SMPD3 and the membrane lipid ceramide. We went on to show slow gating also in red blood cells (RBCs) with implications for understanding hereditary anaemia. We showed that PIEZO1 is important for mechanical sensitivity of calcium-regulated proteases (calpain and ADAM10), nitric oxide production via NOS3, cell interaction via NOTCH1, inflammation and fibrosis via p38, interleukin-6 and tenascin c and cell apoptosis via thrombospondin-2. Through medicinal chemistry studies of Yoda1 (a small-molecule agonist of PIEZO1) we found a Yoda1 antagonist (Dooku1) and new PIEZO1 agonists including one we named Yoda2 with improved reliability, efficacy, potency and physico-chemical properties. To understand the full-length mouse and human channels, their dynamics and responses to force, we performed molecular dynamics simulations in model endothelial and RBC membranes. These models predict complex structural rearrangements and lipid interactions, some of which are now validated by laboratory techniques. In conclusion: PIEZO1 forms an exceptionally sensitive mechanical detector mechanism that responds rapidly to forces such as shear stress. It is important in endothelium, cardiovascular biology generally and physical exercise responses.

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Host:

Andreas Ludwig

Contact:

me3t@ukaachen.de

Speaker

Cheryl L. Stucky

Dept. Cell Biology, Neurobiology and Anatomy

Medical College of Wisconsin, Milwaukee, Wisconsin

https://www.mcw.edu/departments/cell-biology-neurobiology-andanatomy/people/cheryl-stucky-phd

Topics

Keratinocytes are the most abundant cell type in the epidermis across the body and protect our health by keeping bugs out and water in the body. Recent data from several labs show that keratinocytes also play active roles in innocuous and noxious touch sensation in healthy skin. However, little is understood about keratinocytes’ involvement in the development of touch hypersensitivity and chronic pain in neuropathy. This talk will focus on the active roles of keratinocytes in amplifying the signaling during chemotherapy neuropathy and traumatic nerve injury. Furthermore, we recently discovered that a protein called Piezo1 in keratinocytes is necessary for touch sensitivity in normal skin. Our new, unpublished data suggest that Piezo1 in keratinocytes also controls the debilitating touch pain caused by chemotherapy treatment. Given that keratinocytes are distributed across the entire body's surface, interact closely with sensory nerve endings in the skin, and communicate via various neuroactive signaling molecules, understanding their role in neuropathic pain could open new avenues for more effective pain management strategies.

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Host:

Angelika Lampert

Contact:

me3t@ukaachen.de

Topics

Building upon the tradition of previous successful meetings, we like to bring together scientists from different disciplines and from across the world that are interested in physical aspects of cancer progression.

Cancer progression is a complex process involving multiple events that occur across various spatial and temporal scales. There are many great examples showing that physical principles can help to provide a better understanding some of these events. We strongly believe that to unravel the interactions between tumour cells and their niche and to ultimately guide new directions in cancer therapy and diagnostics requires an interdisciplinary approach.

With the Physics of Cancer (PoC) symposium we like to provide a casual setting for scientists across different disciplines to come together in a welcoming atmosphere for lively discussions, stimulation of new ideas, establishment of new collaborations, and also great opportunities for early career scientists. Major topics will be tissue mechanical alterations and diagnostic applications, cell mechanics and mechanosensing, tumor microenvironment interactions, and improved bioengineered models to study relevant aspects of cancer progression in vitro and in vivo.

We have selected a group of excellent speakers from biophysics, cell biology, bioengineering and biomedical backgrounds to embrace the interdisciplinarity of the theme. In addition, we will select several of the best submitted abstracts from early career researchers for oral presentations.

Link:

https://conference.uni-leipzig.de

Speaker

Carsten Grashoff

Institut für Integrative Zellbiologie und Physiologie,

Westfälische Wilhelms-Universität Münster

https://www.uni-muenster.de/Cells-in-Motion/de/people/all/grashoff-c.php

Topics

Recent years have seen an impressive development of molecular force sensing techniques to quantify where and when mechanosensitive proteins are exposed to mechanical loads in cells. Despite their success, it remains challenging to determine how relevant distinct force-bearing linkages are for a given cell biological process. In this seminar, I will summarize our previous work on the development and application of molecular tension sensors allowing the analysis of piconewton-scale forces acting across individual molecules in cells. I will then introduce a novel, genetically encoded, and single-molecule calibrated technology, called molecular optomechanics, to probe the mechanics of individual protein linkages with light. Together, both methods enable the investigation of molecular-scale, mechanobiological processes and facilitate the evaluation of their physiological significance in cells.

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Host:

Rudolf Leube

Institute of Molecular and Cellular Anatomy

Contact:

me3t@ukaachen.de

Topics

MPS have advanced exponentially beyond anyone’s imagination over the last decade. The use spectrum of the new technology has moved within a short time from basic and clinical research to industrial applications in drug discovery and even to the production of data relevant to regulatory decisions. The power of MPS technology to emulate genuine human biology under experimental conditions is likely to make many animal experiments redundant. Dozens of new enterprises have bloomed worldwide on the back of this scientific bandwagon. The International MPS Society (iMPSS), inaugurated at the New Orleans MPS Summit in 2022, together with the European Organ-on-Chip Society (EUROoCS) are bringing the MPS World Summit series to Europe in 2023.

We are delighted and honored to host the next MPS World Summit, this time in Berlin, Germany. The Summit will bring together the academic research community, medical centers, the pharmaceutical, cosmetics, chemical and food industries, regulatory agencies, health foundations, charities, patients associations and policy-makers. NCATS’ generous sponsorship of this conference series may encourage other organizations to act in a similar way. We invite all those interested in connecting, exchanging and learning regarding MPS to join us in Berlin. The city’s unique atmosphere and rich cultural attractions also contribute to making your stay here an event worth remembering.

Link:

https://mpsworldsummit.com/mps-world-summit-2023/

Speaker

Prof. Ferdinand le Noble

Department of Cell and Developmental Biology

Karlsruhe Institute of technology (KIT), Germany

Topics

Organo-typical control of vascular network formation: impact on designing pro- and antiangiogenic therapies

On site:

Spiegelsaal

Flur 3, Raum 1

Uniklinik RWTH Aachen

Host:

Dr. Susanne Fleig

Internal medicine and nephrology

Medical Clinic Vl - Geriatric Medicine

RWTH University Hospital Aachen

Topics

Physical forces across time and length scales play a crucial role in physiology and disease, and the highly multidisciplinary field of mechanobiology has increasing potential to unveil new therapeutic targets. For example, single molecules located in the cell's plasma membrane such as stretch-activated mechanosensitive ion channels mediate fundamental senses including touch. At larger scales, mechanical properties can be markers for the presence of diseases. For instance, the palpation test is oftentime used by clinicians to assert the presence of brest tumors due to the tissue's altered mechanical properties resulting from altered extracellular matrix composition and structure.

We will deliver practical sessions as well as theoretical lectures on techniques scaling from nano/micro scale to bulk approaches to study mechanics in biology and its implications for physiology and disease.

Link:

https://mechanicsinbiology2023.febsevents.org/

Topics

The 11th International Meeting of the Stem Cell Network NRW will take place on May 16/17, 2023 at the “Eurogress” in Aachen, Germany.

As in previous years, both conference days will be filled with lectures by internationally renowned stem cell researchers that address biomedical as well as ethical, legal and social aspects of stem cell research. Of course, there will also be a large industry exhibition, poster sessions for junior scientists to take the opportunity to present their research and a networking event. The language of the international conference is English.

Since 2002, the Stem Cell Network North Rhine-Westphalia organizes its ‘International Meeting’ every two years. With regularly about 600 participants, this is one of the largest congresses in this field of research in Europe.

Registration and Call for Abstracts will open in January 2023.

Link:

https://www.stammzellen.nrw.de/veranstaltungen/international-meeting/2023-11-international-meeting-in-aachen

Speaker

Franziska Lautenschläger

Klemens Rottner

Verena Ruprecht

Manos Mavrakis

Aurélie Bertin

Serge Mostowy

Host:

Sandra Iden

Link:

Zoom-ID: 961 7810 6979

Kenncode: DGZ_FW

Contact:

For questions on this focus workshop series ask Sandra Iden. sandra.iden@uks.eu

Schedule of next events at https://www.zellbiologie.de/workgroups/

Speaker

Janos Vörös

Laboratory of Biosensors and Bioelectronics

ETH Zürich, Switzerland

https://lbb.ethz.ch/

Topics

The traditional way of addressing questions related to the function of the brain involves studying the nervous system of various organism with the argument: “nature optimized these through millions of years of evolution so we should learn how they function by studying the real system”. However, this at the same time means to study something that is highly complex and largely unknown.

Although the tools of neuroscience are becoming more and more advanced, due to the complexity of these systems, it is very difficult to address fundamental questions. Probably this is the reason for the lack of consensus in the field even on seemingly basic questions such as “what is information” and “how is information stored and processed” in the brain. Besides this top-down approach there is also a substantial community (including us) that follows the bottom-up approach1, i.e. trying to learn from small networks of neurons with the advantage that the position and connections of the neurons can be precisely defined and the cells have a good accessibility for recording tools: such as patch clamp2, microelectrode33 or CMOS arrays4, or fluorescence microscopy5.

This talk will introduce new tools that we developed to create and to interact with well-defined neuronal networks. For example, asymmetric PDMS microchannels can be used to guide the axonal growth in the desired direction on top of microelectrode arrays3-6 while nanochannels enable the tuning of the connectivity between pre- and postsynaptic neurons7. This allows studying fundamental neuroscience paradigms and enables the creation of network architectures with real neurons, including human iPSC-derived cells6 towards personalized medicine.

I will also present our attempts to automate building the networks using the FluidFM technology8 and the culturing using custom liquid handling system that also permits reliable changes in the environment including exposure to drugs9.

Overall, the brain-on-a-chip and nerve-on-a-chip technologies presented in this talk are the first necessary step for bottom-up neuroscience, a new approach to study neurons and their networks.

Host:

Angelika Lampert

Institute of Physiology

Link:

Zoom-Link:

https://rwth.zoom.us/j/99189331346?pwd=ck5jZ0pFM3V4bVN4dGYzVDVnR1JEdz09

Meeting-ID: 991 8933 1346

Kenncode: 504063

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Contact:

me3t@ukaachen.de

Speaker:

E. Ada Cavalcanti-Adam

Max Planck Institute of Medical Research, Heidelberg &

University of Bayreuth, Bayreuth

https://www.mr.mpg.de/14057512/adacv

https://www.pci.uni-heidelberg.de//apc/cavalcanti/staff/cavalcanti_cv.html

Topics

Transmembrane receptors, such as integrins and cadherins, convey chemical and mechanical signals to the intracellular compartment. In the first part of my talk, I will present approaches, based on surface micro- and nanopatterning, to control integrin clustering and the assembly of cell-matrix adhesions during cell migration. A particular focus will be on the regulation of molecular and cellular forces in relation to rigidity sensing of the substrate. In the second part of my talk, I will discuss our recent development on the controlled assembly and mechanics of E-cadherins at cell-cell junctions, and how the crosstalk between cell-matrix and cell-cell adhesion might be coordinated at the nanoscale.

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Link:

https://www.stammzellen.nrw.de/veranstaltungen/international-meeting/2023-11-international-meeting-in-aachen

Host:

Laura De Laporte

Contact:

me3t@ukaachen.de

Topics

12:00 - Sara Wickström and Carsten Grashoff

Introduction

12:05 Raphael Reuten PI, University of Freiburg:

Impact of the extracellular matrix on chemokine gradient formation

12:35 - Luis Henrique Corrêa PhD student, Sorokin lab, University of Münster

How Adipocyte Basement Membranes affect metabolism and homeostasis

13:00 - Federica Pennarola PhD student, Cavalcanti Adam lab, MPI for Medical Research

Nanoscale characterization of receptor particle interactions

13:25 - Johanna Ivaska PI, University of Turku

Filopodia in making and breaking barriers

Link:

Zoom-Link:

Meeting-ID: 961 7810 6979

Passcode: DGZ_FW

Contact:

sandra.ide@uks.eu

Speaker:

Elizabeth Rosado Balmayor

Department of Orthopedic, Trauma and Reconstructive Surgery
Uniklinik RWTH Aachen

Topics

mRNA is a new class of drug that can be used to express a therapeutic protein and, in contrast to DNA, is safer and inexpensive. Among its advantages, mRNA will immediately begin to express its encoded protein in the cell cytoplasm. The protein will be expressed for a period of time, after which the RNA is degraded. There is no risk of genetic damage, one of the concerns with DNA. Nevertheless, mRNA application in tissue regeneration and regenerative medicine remains limited. In this case, mRNA must overcome its main hurdles: immunogenicity, lack of stability, and intracellular delivery. Research has been done to overcome these limitations, and the future of mRNA seems promising for tissue repair. This talk will address questions including: What are the opportunities for mRNA to improve outcomes in musculoskeletal tissue repair? What are the key factors and challenges to expediting this technology to patient treatment (beyond COVID-19 vaccination)? 

Link:

Zoom-Link:

https://rwth.zoom.us/j/99189331346?pwd=ck5jZ0pFM3V4bVN4dGYzVDVnR1JEdz09#success

Meeting-ID: 991 8933 1346

Passcode: 504063

Contact:

sandra.ide@uks.eu

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Host:

Rudolf Leube

Institute of Molecular and Cellular Anatomy

Contact:

me3t@ukaachen.de

Speaker:

Francesca Santoro

Faculty of Electrical Engineering and IT, RWTH Aachen

Institute for Biological Information Processing-Bioelectronics, Forschungszentrum Jülich

Topics

The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. The optimal coupling between cells, i.e. neurons, and materials is mainly based on surface interaction, electrical communication and sensing.

In the last years, many efforts have been devoted to the engineering of materials to recapitulate both the environment (i.e. dimensionality, curvature, dynamicity) and the functionalities (i.e. long and short term plasticity) of the neuronal tissue to ensure a better integration of the bioelectronic platform and cells.

On the one hand, here we explore how the transition from planar to pseudo-3D nanopatterned inorganic and organic materials have introduced a new strategy of integrating bioelectronic platforms with biological cells under static and dynamic conditions.. On the other hand, we investigate how organic semiconductors can be exploited for recapitulating electrical neuronal functions such as long term and short term potentiation. In this way, both the topology and the material functionalities can be exploited for achieving in vitro biohybrid platforms for neuronal network interfacing.

Link:

Zoom-Link:

https://rwth.zoom.us/j/91504326004?pwd=R2dvWEcyQmpCenNNZDRYWHMzVExLUT09

Meeting-ID: 915 0432 6004

Kenncode: 334655

Host:

Rudolf Leube

Institute of Molecular and Cellular Anatomy

Contact:

me3t@ukaachen.de

Topics

Our aim is to create a platform for leaders in organoid research to discuss the advancements in 3D culture systems.

Speakers:

Sina Bartfeld - TU Berlin, Germany

Daniel Besser - German StemCell Network, Berlin, Germany

Sylvia Boj - Hubrecht Organoid Technology, Netherlands

Katharina Debowski - STEMCELL Technologies

Mina Gouti - Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany

Arne Hansen - UKE Hamburg, Germany

Leopold Koenig - TissUse GmbH, Berlin, Germany

Matthias Lutolf - EPFL's Institute of Bioengineering, Switzerland 

Roxana Micsik - STEMCELL Technologies

Carlos Mota - MERLN, Maastricht University, Netherlands

Peter Ponsaerts - University of Antwerp, Belgium

Anja Trillhaase - Institute for Cardiogenetics, Lübeck University, Germany

Casper van der Ven - CellBricks GmbH, Berlin

Link:

https://www.medicalschool-hamburg.de/caos/

Speaker

Josef A. Käs

Faculty of Physics and Earth Sciences

University of Leipzig

https://home.uni-leipzig.de/pwm/web/

Topics

Distant metastasis is probably the most lethal hallmark of cancer. Due to a lack of suitable markers, cancer cell motility only has a negligible impact on current diagnosis. Based on cell unjamming we derive a cell motility marker for static histological images. This enables us to sample huge numbers of breast cancer patient data to derive a comprehensive state diagram of unjamming as a collective transition in cell clusters of solid tumors. As recently discovered, cell unjamming transitions occur in embryonic development and as pathological changes in diseases such as cancer. No consensus has been achieved on the variables and the parameter space that describe this transition. Cell shapes or densities based on different unjamming models have been separately used to describe the unjamming transition under different experimental conditions. Moreover, the role of the nucleus is not considered in the current unjamming models. Mechanical stress propagating through the tissue mechanically couples the cell nuclei mediated by the cell's cytoplasm, which strongly impacts jamming.

Based on our exploratory retrospective clinical study with N=1,380 breast cancer patients and vital cell tracking in patient-derived tumor explants, we find that the unjamming state diagram depends on cell and nucleus shapes as one variable and the nucleus number density as the other that measures the cytoplasmic spacing between the nuclei. Our approach unifies previously controversial results into one state diagram. It spans a broad range of states that cancer cell clusters can assume in a solid tumor. We can use an empirical decision boundary to show that the unjammed regions in the diagram correlate with the patient's risk for metastasis.

We conclude that unjamming within primary tumors is part of the metastatic cascade, which significantly advances the understanding of the early metastatic events. With the histological slides of two independent breast cancer patients' collectives, we train (N=688) and validate (N=692) our quantitative prognostic index based on unjamming regarding metastatic risk. Our index corrects for false high- and low-risk predictions based on the invasion of nearby lymph nodes, the current gold standard. Combining information derived from the nodal status with unjamming may reduce over- and under-treatment. 

Host:

Rudolf Leube

Institute of Molecular and Cellular Anatomy

Link:

Zoom-Link:

https://rwth.zoom.us/j/99189331346?pwd=ck5jZ0pFM3V4bVN4dGYzVDVnR1JEdz09

Meeting-ID: 991 8933 1346

Kenncode: 504063

On site:

Seminarraum B1.72

DWI – Leibniz-Institut für Interaktive Materialien

Forckenbeckstraße 50, 52074 Aachen

Contact:

me3t@ukaachen.de

Speaker

Jennifer L. Young

Assistant Professor, Department of Biomedical Engineering

Principal Investigator, Mechanobiology Institute

National University of Singapore, Singapore

https://www.mbi.nus.edu.sg/jennifer-young/

Topics

It is well appreciated that extracellular cues stemming from the matrix dictate a multitude of cellular functions, from motility to stem cell differentiation. Yet, the extracellular environment is inherently complex and thus hinders our full understanding of specific matrix-based contributions to cellular behavior. Our work focuses specifically on the context of age-related matrix remodeling and engineering materials capable of recapitulating matrix properties in vitro at both the micro and nano length scales. This talk will highlight some of our material approaches to control cell-matrix interactions in the context of cardiac aging and mechanobiology. In the first, we describe methods for developing tunable stiffness gradient polyacrylamide (PA) hydrogels using a two-step polymerization method. These platforms are capable of spanning the diverse physiological and pathological mechanical landscapes present in the heart for gaining a more thorough understanding of mechanosensitive processes on cardiac function. Our second material strategy is able to maintain matrix composition and organization independent of matrix stiffness through hydrogel-stabilized decellularized cardiac tissue slices of young and aged mouse hearts. Subsequent culture of cardiac fibroblasts (young and aged) show that the matrix ‘age’ can outweigh matrix mechanics in driving fibroblast activation. In our third approach, we mimic ligand presentation at the nanoscale using Block Copolymer Micelle Nanolithography (BCMN), in which highly ordered gold nanoparticle arrays are deposited onto surfaces with defined interparticle spacing. These particles are subsequently functionalized with peptides and we find that cardiac cell adhesion and mechanomarker expression are enhanced at 35 vs. 50 nm interparticle spacing. Our strategies ultimately aim to interrogate the cell-matrix interface using highly defined biomaterial systems at different length scales that can inform future matrix-based treatment strategies.

Host:

Jacopo Di Russo

Institute of Molecular and Cellular Anatomy

Link:

Zoom-Link:

https://rwth.zoom.us/j/99189331346?pwd=ck5jZ0pFM3V4bVN4dGYzVDVnR1JEdz09

Meeting-ID: 991 8933 1346

Kenncode: 504063

Contact:

me3t@ukaachen.de

Speaker:

Dr. Sean Blamires,

Theodore von Kármán Fellow, University of New South Wales (UNSW), Sydney, Australia

Dr Sean Blamires is a Research Fellow at UNSW and Visiting Fellow at the Centre for Audio,

Acoustics and Vibration at the University of Technology, Sydney.

His research is on the biochemistry, and biomechanics of spider and insect silks.

Affiliation: 1School of Biological, Earth and Environmental Science & NMR Facility,

Mark Wainwright Analytical Centre, University of New South Wales, Sydney NSW 2052,

2School of Mechanical and Mechatronic Engineering, University of Technology, Sydney, NSW 2007

Topics

The silks of silkworms and spiders is a proteinaceous secretion that has a combined strength and toughness that exceeds all other natural fibers. It additionally has a unique set of optical, acoustic and conductive properties. There is accordingly immense interest among bioengineers in developing a range of synthetic materials that mimic silk’s properties. A concerted effort has been made toward understanding the mechanisms by which different silks acquire their properties, and this has uncovered links between gene expression, protein structure, and fibre function in many silks. Nevertheless, we are constantly finding instances where the associations between genes, proteins, and fibre performance are decoupled, implying that nano-scale variations can have noticeable effects at the macro-scale. We nevertheless know little about the structural and behavioural variability between and within fibres at nano-scales. I explore here some of recent work in my laboratory on silkmoth silk, spider major ampullate silk, and spider cribellate silk, to show how variations across threads can be influenced by nano-scale features, including how silk threads of a few nano-metres in diameter can retain certain functional properties. 

On site:

NGP2,

Hörsaal A005

Forckenbeckstraße 51, 52074 Aachen

Host:

Jacopo Di Russo

Institute of Molecular and Cellular Anatomy