Reciprocal intra- and extra-cellular polarity enables deep mechanosensing through layered matrices

被引：2

作者：

Walter, Christopher ^{[1
]}

Mathur, Jairaj ^{[1
]}

Pathak, Amit ^{[1
]}

机构：

[1] Washington Univ St Louis, Dept Mech Engn & Mat Sci, St Louis, MO 63110 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 04期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

CELL-MIGRATION; ELASTICITY; STIFFNESS; MODEL; PROTEOLYSIS; CHEMOTAXIS; PLASTICITY; MOLECULES; MOVEMENT; BLOCKING;

D O I：

10.1016/j.celrep.2023.112362

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Adherent cells migrate on layered tissue interfaces to drive morphogenesis, wound healing, and tumor inva-sion. Although 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 because of "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 abrogates 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.

引用

页数：24