M.Sc Thesis


M.Sc StudentWeil Hila
SubjectAdhesion-Free Motility: Characterization of a Novel Mode
of Cell Migration
DepartmentDepartment of Biology
Supervisors ASSOCIATE PROF. Tom Shemesh
DR. David Meiri
Full Thesis textFull thesis text - English Version


Abstract

Cell motility is a key factor in various processes such as cancer metastasis, immune response, and wound healing.  The mode of cell migration depends on the chemical, mechanical and geometrical properties of the extra-cellular environment. While adhesive modes of motility are well understood, the mechanisms underlying migration in the absence of cell-matrix and cell-cell adhesions are yet to be understood.  Here, we present a novel high-resolution microfluidic assay for the study of cellular motility in confined environments. We employ this setup to study cellular crawling motility under different conditions, where cellular ability to exert traction forces on their environment is modulated.  Our results uncovered a previously uncharacterized, adhesion-free, motility mode in MDA-MB 231 breast cancer cells. In the absence of traction forces and low friction environments, confinement alone is sufficient to enable a non-adhesive migration phenotype. We find that under asymmetric confinement conditions, non-adhesive cellular migration becomes polarized, with a directionality that is determined by extra-cellular geometrical cues, as well as by cellular characteristics, such as cell size. Our results suggest that topography cues play a significant role in regulating cell behaviors. Understanding the mechanisms governing cell migration in confinement is critical to fully understand key processes, such as the plasticity of cancer cells motility modes. Our micro-channel essay may be used in further studies for characterization of cellular response to varied confinement conditions.