Dynamics and mechanics of wound healing

• Applicants: Dr. Alexey Chizhik; Professor Dr. Andreas Janshoff
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431012826

Cohesive sheets formed by epithelial cells play an important role in tissue development, secretion, transcellular transport, barrier formation and infection prevention and control. Therefore, wounds or defects in epithelia pose a severe threat as they might lead to infection and eventually to death of the organism. The ability to quickly repair these physical voids is a crucial feature of individual cells and multicellular systems requiring a concerted interaction of cells as a collective and with their environment. Within this project, we address the collective action of cells in response to externally imposed injuries that generate transient gaps or defects in an epithelial cell monolayer. Among parameters such as tension, it is indisputable that the cell-substrate dynamics plays a pivotal role in wound healing. Efficient collective cell movement requires cells to exert pushing and pulling forces though interaction with the substrate. We will use cell-substrate distance as a crucial readout parameter of the interaction of cells with the underlying extracellular matrix. We will primarily employ MIET microscopy providing nanometer-precision in z-direction paired with label-free cell adhesion noise spectroscopy, which both allow us to address the spatiotemporal dynamics of the cell-substrate cleft. Specifically, we plan to investigate how the cell-substrate distance of cells adjacent to the wound changes as a function of cell type, gap size, and geometry of the void. We are also interested in exploring the spatiotemporal correlation of the distance between cell and substrate on length scales ranging from subcellular structures up to supracellular ensembles of cells further away from the defect. Concretely, we plan to measure the interplay of dynamics (motility) and mechanics (cortical tension) of cell monolayers as well as the mode of void closure that is typically classified as either lamellipodia-driven or following a purse string mechanism. Thereby we expect to obtain insight into the mechanism how cells transmit forces in an epithelial sheet and over what distance this information can be relayed. Fluctuation analysis of the out-of-equilibrium noise in the cell-substrate distance generated by active processes inside the cells will widen the parameter space to address the physics of active matter in a more quantitative fashion over many length scales using living cells connected to each other.

• DFG Programme: Research Grants