Abstract Cells are known to continuously remodel their local extracellular matrix (ECM) and in a reciprocal way, they can also respond to mechanical and biochemical properties of their fibrous environment. In this study, we measured how stiffness around dermal fibroblasts (DFs) and human fibrosarcoma HT1080 cells differs with concentration of rat tail type 1 collagen (T1C) and type of ECM. Peri-cellular stiffness was probed in four directions using multi-axes optical tweezers active microrheology (AMR). First, we found that neither cell type significantly altered local stiffness landscape at different concentrations of T1C. Next, rat tail T1C, bovine skin T1C and fibrin cell-free hydrogels were polymerized at concentrations formulated to match median stiffness value. Each of these hydrogels exhibited distinct fiber architecture. Stiffness landscape and fibronectin secretion, but not nuclear/cytoplasmic YAP ratio differed with ECM type. Further, cell response to Y27632 or BB94 treatments, inhibiting cell contractility and activity of matrix metalloproteinases, respectively, was also dependent on ECM type. Given differential effect of tested ECMs on peri-cellular stiffness landscape, treatment effect and cell properties, this study underscores the need for peri-cellular and not bulk stiffness measurements in studies on cellular mechanotransduction.
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Cells exploit a phase transition to mechanically remodel the fibrous extracellular matrix
Through mechanical forces, biological cells remodel the surrounding collagen network, generating striking deformation patterns. Tethers—tracts of high densification and fibre alignment—form between cells, thinner bands emanate from cell clusters. While tethers facilitate cell migration and communication, how they form is unclear. Combining modelling, simulation and experiment, we show that tether formation is a densification phase transition of the extracellular matrix, caused by buckling instability of network fibres under cell-induced compression, featuring unexpected similarities with martensitic microstructures. Multiscale averaging yields a two-phase, bistable continuum energy landscape for fibrous collagen, with a densified/aligned second phase. Simulations predict strain discontinuities between the undensified and densified phase, which localizes within tethers as experimentally observed. In our experiments, active particles induce similar localized patterns as cells. This shows how cells exploit an instability to mechanically remodel the extracellular matrix simply by contracting, thereby facilitating mechanosensing, invasion and metastasis.
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- Award ID(s):
- 1749400
- NSF-PAR ID:
- 10213871
- Date Published:
- Journal Name:
- Journal of The Royal Society Interface
- Volume:
- 18
- Issue:
- 175
- ISSN:
- 1742-5662
- Page Range / eLocation ID:
- 20200823
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Cells are known to continuously remodel their local extracellular matrix (ECM) and in a reciprocal way, they can also respond to mechanical and biochemical properties of their fibrous environment. In this study, we measured how stiffness around dermal fibroblasts (DFs) and human fibrosarcoma HT1080 cells differs with concentration of rat tail type 1 collagen (T1C) and type of ECM. Peri-cellular stiffness was probed in four directions using multi-axes optical tweezers active microrheology (AMR). First, we found that neither cell type significantly altered local stiffness landscape at different concentrations of T1C. Next, rat tail T1C, bovine skin T1C and fibrin cell-free hydrogels were polymerized at concentrations formulated to match median stiffness value. Each of these hydrogels exhibited distinct fiber architecture. Stiffness landscape and fibronectin secretion, but not nuclear/cytoplasmic YAP ratio differed with ECM type. Further, cell response to Y27632 or BB94 treatments, inhibiting cell contractility and activity of matrix metalloproteinases, respectively, was also dependent on ECM type. Given differential effect of tested ECMs on peri-cellular stiffness landscape, treatment effect and cell properties, this study underscores the need for peri-cellular and not bulk stiffness measurements in studies on cellular mechanotransduction.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1098/rsif.2020.0823
