Reciprocal Intra- and Extra-Cellular Polarity Enables Deep Mechanosensing Through Layered Matrices
49 Pages Posted: 10 Nov 2022 Publication Status: Published
More...Abstract
Adherent cells migrate on layered tissue interfaces to drive morphogenesis, wound healing, and tumor invasion. While stiffer surfaces are known to enhance cell migration, it remains unclear whether cells sense basal stiff environments buried under softer, fibrous matrix. Using layered collagen-polyacrylamide gel systems, we unveil a migration phenotype driven by cell-matrix polarity. Here, cancer (but not normal) cells with stiff base matrix generate stable protrusions, faster migration, and greater collagen deformation due to ‘depth mechanosensing’ through the top collagen layer. Cancer cell protrusions with front-rear polarity produce polarized collagen stiffening and deformations. Disruption of either extracellular or intracellular polarity via collagen crosslinking, laser ablation, or Arp2/3 inhibition independently abrogate depth-mechanosensitive migration of cancer cells. Our experimental findings, validated by lattice-based energy-minimization modeling, present a cell migration mechanism whereby polarized cellular protrusions and contractility are reciprocated by mechanical extracellular polarity, culminating in a cell type-dependent ability to mechanosense through matrix layers.
Funding Information: We acknowledge financial support from following sources: National Institutes of Health grant R35GM128764 (to A.P.) and National Science Foundation, Science and Technology Centers, Center for Engineering MechanoBiology grant CMMI:154857 (to A.P.)
Declaration of Interests: None to declare.
Keywords: cell polarity, Cell migration, extracellular matrix polarity, layered matrix, Collagen, atomic force microscopy, laser ablation, depth sensing, mechanosensing, mechanobiology
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