Sensing Traction Force on the Matrix Induces Cell–Cell Distant Mechanical Communications for Self-Assembly

Abstract

The long-range biomechanical force propagating across large scale may reserve the capability to trigger coordinative responses within cell population such as during angiogenesis, epithelial tubulogenesis, and cancer metastasis. How cells communicate in a distant manner within the group for self-assembly remains largely unknown. Here we found that airway smooth muscle cells (ASMCs) rapidly self-assembled into well-constructed network on 3D Matrigel containing type I collagen (COL), which relied on long-range biomechanical force across the matrix to direct cell-cell distant interactions. Similar results happened by HUVEC cells to mimic angiogenesis. Interestingly, single ASMCs initiated multiple extended protrusions precisely pointing to neighboring cells in distance, depending on traction force sensing. Separate ASMCs sensed each other to move directionally on both non-fibrous Matrigel and more efficiently when containing fibrous COL, but lost mutual sensing on fixed gel or coated glass due to no longrange force transmission. Beads tracking assay demonstrated distant transmission of traction force, and finite element method modeling confirmed the consistency between maximum strain distribution on matrix and cell directional movements in experiments. Furthermore, ASMCs recruited COL from the hydrogel to build fibrous network to mechanically stabilize cell network.Our results revealed for the first time that cells can sense traction force transmitted through the matrix to initiate cell-cell distant mechanical communications, resulting in cell directional migration and coordinative self-assembly with active matrix remodeling. As an interesting phenomenon, cells sound able to 'make phone call' via long-range biomechanics, which implicates physiological importance such as for tissue pattern formation.

Mechanical communication-induced cell directional migration and branching connections mediated by calcium channels, integrin β1 and N-cadherin

“…In this work, we tried to study the primary mechanosensing components for cell-cell distant mechanical interactions. Based on the experimental model from our recent work [24], we characterized cell directional migration and network assembly to measure cell-cell mechanical attractions, which was applied to identify cellular mechanosensitive components.…”

“…The preparation processes of PDMS mold and cell network culture have been introduced in our recent work [24]. Briefly, a thin layer of PDMS (∼600 μm in thickness) was generated by mixture of the two liquid components from the Sylgard 184 kit (Dow Corning).…”

“…As described recently [24], the epi-microscopy system (Zeiss) was equipped with the X-Y-Z control stage for multi-position function, fine auto-focusing for time-lapse imaging, and temperature (37°C)-CO2 (5%) chamber to maintain cell culture conditions.…”

“…Our previous work demonstrated that cell mutual attraction and migration rely on sensation of traction force on the hydrogel which is derived from cell contraction [24].…”

“…In this work, we applied the experimental model of mechanical communication from our recent study [24], and investigated the mechanosensitive pathways in regulating the mechanical attractions and cell connection stability. Our work identified the critical functions of calcium channels on the ER membranes and integrin signal along with actomyosin contraction in cell distant mechanical attractions, and Ncadherin in stabilizing cell-cell connections.…”