Modeling shapes and traction forces of steady moving and perturbed cells

• Applicant: Dr. Falko Ziebert
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246963360

The substrate-based crawling motion of eukaryotic cells is essential for many biological functions, both during development and in the mature organism, and its dysfunction is involved in several pathologies. On the other hand, motile cells are a natural realization of active, self-propelled particles, a very active topic in nonequilibrium physics. Although a comprehensive understanding of substrate-based motility remains elusive, progress has been achieved recently in its modeling on the level of a whole cell. The aim of the original proposal was to develop a modeling framework that includes all key physical aspects of cell crawling and that would allow a simultaneous prediction of the shapes of motile cells and the traction force patterns they exert on the substrate, being the physical traces of the global force balance. During the first funding period we developed a model accounting for spatially resolved traction forces, allowing for a wide diversity of cell shapes and dynamics. In addition, reacting to current experimental research directions, we improved the description of the membrane by including its tension, which acts as a global force regulator counteracting actin polymerization, and generalized the model to describe several cells, allowing to study collective cellular motion. We now have all the pieces in hand that combined will allow us to achieve the original goal. In this follow-up proposal for a third year of funding we will assemble the modeling parts and refine and adjust them to the experimental data from our external collaborator (A. Verkhovsky, Lausanne) on steady moving and polarizing (i.e. starting to move) keratocyte cells. In addition, based on the generalization to several cells, we will study encounters of cells and cell fragments, where experiments have just been started. Investigating such collisions will further strengthen the model s fidelity, and allow to study the cellular response to external perturbations in a biologically relevant context that becomes increasingly explored (cf. collective motion, crowding). Apart from the physics of single and small ensembles of moving cells, the model under development will also be of profit for other, biological and artificial, driven soft systems.

• DFG Programme: Research Grants
• International Connection: Switzerland, USA
• Cooperation Partners: Professor Dr. Igor Aronson; Dr. Alexander Verkhovsky, Ph.D.