סמינר מחלקתי Ayelet Lesman
School of Mechanical Engineering Seminar
Monday, March 30, 2015 at 15:00
Wolfson Building of Mechanical Engineering, Room 206
Mechanical Interaction between Cells and their Surrounding 3D Fibrous Environments
Ayelet Lesman
Division of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, CA.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
The forces cells apply to their surroundings control biological processes such as growth and migration. In the past 20 years, a number of experimental techniques have been developed to measure such cell tractions. These approaches have primarily measured the tractions applied by cells to synthetic two-dimensional substrates, which do not mimic physiological conditions for most cell types. Our work aimed at developing and applying an experimental technique for quantifying cellular forces in a natural, fibrous 3D gel matrix. The approach is based on confocal time-lapse imaging to observe cells and their surrounding matrix in three dimensions. We then use a digital volume correlation (DVC) approach to map the displacements of the matrix in space and time (x, y, z, and t). Tracking the movement of the matrix is a key step in this process. I describe two ways of tracking, either by embedding fluorescent particles in the gel or by directly imaging the fiber structure of the gel. The direct imaging approach allows to discern the local deformation or reorientation of the gel fibers in response to cellular forces (details we cannot achieve when using particles).
The 3D traction measurement approach is used to investigate how cells mechanically interact with the matrix in biologically relevant processes such as division, invasion and cell-cell interaction. During division, a single mother cell undergoes a drastic morphological change to split into two daughter cells. We find that tensile forces applied by dividing cells on the matrix, far from the cell body, oriented the cell division axis. Cell invasion into a 3D matrix is the first step required for cell migration in three dimensions, and is prerequisite for cancer metastasis. Using our direct approach of imaging matrix fibers to compute displacements, we find that cells generate large plastic deformation of the matrix by applying both pushing and pulling forces. Lastly, our measurements provide insight into mechanical communication between cells. We measured the propagation of displacements induced by contractile cells in fibrous gels and found that they are effective over longer distances than predicted by linear elastic models. Finite element simulations suggest that fiber buckling is a key feature of the fibrous network responsible for this effect. This helps rationalize our observations that cells separated by large distances (~100-200 microns) are coupled by aligned, dense fibers in tether-like bends. We suggest that cells may exploit the non-linear properties of the fibrous environment to communicate over long ranges by sensing the deformation induced by their neighbors.
