The Balance between Actomyosin Contractility and Microtubule Polymerization Regulates Hierarchical Protrusions That Govern Efficient Fibroblast-Collagen Interactions

ACS Nano. 2020 Jul 28;14(7):7868-7879. doi: 10.1021/acsnano.9b09941. Epub 2020 Apr 20.


Fibroblasts undergo a critical transformation from an initially inactive state to a morphologically different and contractile state after several hours of being embedded within a physiologically relevant three-dimensional (3D) fibrous collagen-based extracellular matrix (ECM). However, little is known about the critical mechanisms by which fibroblasts adapt themselves and their microenvironment in the earliest stage of cell-matrix interaction. Here, we identified the mechanisms by which fibroblasts interact with their 3D collagen fibrous matrices in the early stages of cell-matrix interaction and showed that fibroblasts use energetically efficient hierarchical micro/nano-scaled protrusions in these stages as the primary means for the transformation and adaptation. We found that actomyosin contractility in these protrusions in the early stages of cell-matrix interaction restricts the growth of microtubules by applying compressive forces on them. Our results show that actomyosin contractility and microtubules work in concert in the early stages of cell-matrix interaction to adapt fibroblasts and their microenvironment to one another. These early stage interactions result in responses to disruption of the microtubule network and/or actomyosin contractility that are opposite to well-known responses to late-stage disruption and reveal insight into the ways that cells adapt themselves and their ECM recursively.

Keywords: cell protrusion; cell−matrix early interaction; collagen remodeling; dendritic morphology; fibrous traction force microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actomyosin*
  • Cell Movement
  • Collagen*
  • Extracellular Matrix
  • Fibroblasts
  • Microtubules
  • Polymerization


  • Collagen
  • Actomyosin