Mechanobiology in Epithelial
3D Tissue Constructs

CM 1 - Topics and presenters of the interdisciplinary course
"Concepts and technologies in cell and tissue mechanics – An integrated view from physicochemical, engineering, biological and medical perspectives" (*Competent senior postdocs from the participating groups; **Local experts; *** Invited experts; affiliations see below)
  1st Year: Basic aspects of epithelial mechanobiology
Teaching module 1: Introduction to basic concepts in biophysics and cell biology (alternative choice depending on background)
Biological physics: review of statistical physics, continuum mechanics, fluid dynamics at small scales,
theory of diffusion for biological systems
A.-S. Smith, R. Merkel,
U. Schnakenberg
Basics in cell biology and histology: cellular compartments, cytoskeleton and adhesion, extracellular matrix, cell communication, cell cycle, concepts in histology and features of epithelial differentiation V. Buck*, R. Leube, A. Ludwig, N. Schwarz*, R. Windoffer*
Teaching day 1: A bottom-up engineering approach to the mechanical components of epithelial assemblies
Mechanical properties of molecules (proteins & polymers; deformability, unfolding by forces), of molecular bonds
(force induced dissociation, catch & slip bonds), and molecular assemblies (filaments and networks)
R. Merkel, R. Göstl**
Cell-matrix and cell-cell-adhesion as examples of dynamic supramolecular aggregates, also force-induced breakage of adhesions (tape peeling models, molecular models) R. Merkel, A.-S. Smith
Mechanical properties of individual cells, cellular assemblies and extracellular matrix R. Merkel, R. Leube, A. Ludwig, R. Windoffer*, H. Fischer
Teaching day 2: Formation and dynamics of complex epithelial structures
Cell migration: Fundamental epithelial properties in health and disease R. Leube, A. Ludwig, R. Merkel
Cyst formation and tubulation: Key features of epithelial dynamics during development and differentiation - Mechanics of plates, cylinders and shells R. Merkel, R. Leube
Organoids as functional tissue equivalents R. Leube, N. Schwarz*, W. Wagner
Teaching day 3: Hallmarks of epithelial systems
Surface specializations, stratum specificity and cellular heterogeneity R. Leube, N. Schwarz*
The extracellular matrix in molecular interplay with and as a mechanical counterbalance of epithelia G. Klein***, E. Noetzel-Reiss*
Hydrodynamic aspects in epithelial cell biology: Basics in rheology at small length scales: low Reynolds numbers hydrodynamics, Newtonian and non-Newtonian fluids; microfluidic devices to mimic the epithelium-liquid and
epithelium-air interface
S. Jockenhövel, U. Schnakenberg
Teaching day 4: Force as a signal in epithelial tissues: perception, transduction and response
Structures and molecules for mechanosensing A. Ludwig, W. Wagner
Mechanically induced signaling pathways signal transduction A. Ludwig, A. Sechi**
Neuronal force sensing in epithelia A. Lampert, A. Binshtok***
  2nd Year: Experimental approaches in epithelial mechanobiology
Teaching day 5: Biophotonics
Principles and choices in light microscopy G. Müller-Newen**,  R. Windoffer*
Monitoring processes in 3D V. Buck*, R. Leube, E. Noetzel-Reiss*
Genetically-encoded molecular force sensors and optogenetic actuators R. Göstl**, R. Leube
Teaching module 2: Analysis of images and statistical analysis of cellular properties and processes
Introduction to data analysis (statistical distributions, accuracies, hypothesis testing)
- Basic algorithms for microscopy image analysis
- Principles of multidimensional data analysis 
A.-S. Smith, N. Aliee*, S. Uhlig
Teaching day 6: Tools for force application
Magnetic and optical tweezers U. Schnakenberg, R. Windoffer
AFM, cell stretcher and laser nanosurgery B. Hoffmann*, R. Merkel
Magnetogenetics for control of mechanobiological processes C. Monzel***
Teaching day 7: Biomaterials and tissue engineering
Biomaterials: Natural and synthetic hydrogels with defined mechanical properties L. De Laporte, H. Fischer,
S. Jockenhövel
Tissue engineering: Role of fiber-based scaffolds and bioreactors for 3D epithelial tissue constructs S. Jockenhövel, P. Mela**, S. Singh**
Tissue engineering: Bioprinting composite tissues H. Fischer
Teaching day 8: Bioinformatics for epithelial mechanobiology
Working with big data and supercomputers K. Krajsek***
Machine learning K. Krajsek***
Computational pathway and network analysis I. Costa**
  3rd Year: Current issues in epithelial mechanobiology
Teaching module 3: Building numerical models for biological processes and computational methods
Introduction to computational modeling – basic simulation algorithms for energy and free energy minimizers , simple and kinetic MC, Langevin and Newton dynamics A.-S. Smith, M. Aliee*
Teaching day 9: Tissue mechanics as a regulator of epithelial differentiation and function
Stem cell differentiation in defined mechanical niches S. Neuss-Stein**; W. Wagner
Trophoblast invasion and connective tissue stiffness V. Buck*, I. Claßen-Linke*
Metastasis and connective tissue stiffness E. Noetzel-Reiss*, W. Wagner
Teaching day 10: Technological advancements part 1
State of the art and challenges in functional tracheal implant fabrication H. Fischer, S. Jockenhövel, L. Thiebes*
State of the art and challenges in biopriniting of epidermal equivalents H. Fischer
State of the art and challenges in functionalized cell substrates L. De Laporte
Teaching day 11: Technological advancements part 2
State of the art and challenges in photonic scaffold production technologies and photosensitive biomaterials S. Jockenhövel; N. Nottrodt**
Genetic engineering of primary cells and cell lines for applications in mechanobiology A. Ludwig, W. Wagner
The ins and outs of omics J. Jankowski**
Teaching day 12: Epithelial mechanobiology in health and disease (teaching day 4)
Alternative mechanoresponses in genetic skin disease A. Lampert, R. Leube, N. Schwarz*
Mechanical stress and inflammation A. Ludwig, K. Reiss*, S. Uhlig
Altered force distribution in tissue invasion V. Buck*, R. Leube
Wrap-up (half day): Summary and reflection of curriculum
Critical assessment and evaluation of the entire module with concrete suggestions for improvement Chairs: Student representatives and spokespersons
Affiliation of non-ME3T lecturers (in alphabetical order):
* Members of participating departments/institutes: M. Aliee (PULS), V. Buck (MOCA), I. Claßen-Linke (MOCA), D. F. Duarte Campos (ZWBF), B. Hoffmann (FZJ), E. Noetzel-Reiss (FZJ), K. Reiss (Pharmacology), N. Schwarz (MOCA), L. Thiebe (Bio Tex), R. Windoffer (MOCA)
** Local researchers: I. Costa (Computational Biology), R. Göstl (DWI), J. Jankowski (IMCAR), P. Mela (Institute of Applied Medical Engineering), G. Müller-Newen (Biochemistry), S. Neuss-Stein (Pathology and Biomedical Engineering), N. Nottrodt (Fraunhofer ILT), A. Sechi (Institute for Biomedical Engineering), S. Singh (DWI)
*** External guests: A. Binshtok (The Hebrew University Medical School, Jerusalem), G. Klein (University of Tübingen), K. Krajsek (FZJ), C. Monzel (University of Düsseldorf)