Vimentin intermediate filaments mediate cell shape on visco-elastic substrates

Abstract

The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk amongst the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear. To investigate vimentin's role in substrate sensing, we designed polyacrylamide hydrogels that mimic the elastic and viscoelastic nature of in vivo tissues. Using wild-type and vimentin-null mouse embryonic fibroblasts, we show that vimentin enhances cell spreading on viscoelastic substrates, even though it has little effect in the limit of purely elastic substrates. Our results provide compelling evidence that the vimentin cytoskeletal network is a physical modulator of how cells sense and respond to mechanical properties of their extracellular environment.

Determination by Relaxation Tests of the Mechanical Properties of Soft Polyacrylamide Gels Made for Mechanobiology Studies

“…These materials, indeed, look more similar to real tissues, are dissipative in nature, and restore native cellular behavior in culture [ 21 ]. By experimentally controlling the viscous and elastic phases separately [ 22 ], biomaterials also help elucidate complex mechanobiology phenomena and will certainly impact the field further [ 23 ], as cells sense and respond to dissipative substrates [ 24 ]. Storage and loss moduli must then both be reported when characterizing mechanical properties, as cells respond to both elastic and viscous parts of their naturally viscoelastic substrates modifying their internal structures and nuclear envelope [ 25 ].…”

Intermediate filaments: Integration of cell mechanical properties during migration

“…I-II Keratins ↑ Cell stiffness (Seltmann et al, 2013a;Ramms et al, 2013;Laly et al, 2021) ↑ Cell resilience (Seltmann et al, 2013a) ↓ Traction forces (Wang et al, 2020) ↑ Stress fibers (Fujiwara et al, 2016;Wang et al, 2020) ↑ Nuclear mechanotransduction (Laly et al, 2021) ↑ Mechanosensitive cell responses (Weber et al, 2012;Mariani et al, 2020;Laly et al, 2021) ↑ Cell-cell adhesion (Jacob et al, 2018;Wang et al, 2018) ↑ Cell-BM adhesion (Wang et al, 2018;Wang et al, 2020) ↓ Cell migration (Weber et al, 2012;Seltmann et al, 2013a;Seltmann et al, 2013b) III Vimentin GFAP Desmin ↑ Cell stiffness (Brown et al, 2001;Rathje et al, 2014;Charrier et al, 2018) ↑ Cell resilience (Sharma et al, 2017;Hu et al, 2019) ↑ Cell viability (Hu et al, 2019) ↓ Nucleus deformation (Patteson et al, 2019) ↓ NE rupture (Patteson et al, 2019) ↑ Traction forces (De Pascalis et al, 2018) ↑ Stress fibers (Jiu et al, 2015;Jiu et al, 2017;De Pascalis et al, 2018) ↑ Cell stiffness (Charrier et al, 2018) ↑ Mechanosensitive cell responses (Swoger et al, 2020) ↑ FAs lifetime (De Pascalis et al, 2018) ↑ Cell adhesion (Ivaska et al, 2005;Havel et al, 2015;Kim et al, 2016) ↑ Cell migration (Helfand et al, 2011;…”

“…The role of vimentin in mechanosensing was recently studied by Patteson AE group by designing hydrogels with controlled elastic and viscoelastic material properties. Cells lacking vimentin showed an impaired spreading on viscous substrates (Swoger et al, 2020) (Table 1). Changes in substrate viscoelasticity, but not in substrate elasticity, led to a reorganisation of vimentin filaments into a mesh-like cage in the perinuclear area, which may indirectly affect mechanosensitive nuclear responses.…”

Determination by Relaxation Tests of the Mechanical Properties of Soft Polyacrylamide Gels Made for Mechanobiology Studies

“…These materials indeed look more similar to real tissues, dissipative in nature, and restore native cellular behavior in culture [20]. By experimentally controlling the viscous and elastic phases separately [21], biomaterials also help elucidate complex mechanobiology phenomena and will certainly impact the field further [22], as cells sense and respond to dissipative substrates [23]. Storage and loss moduli must then both be reported when characterizing mechanical properties, as cells respond to both elastic and viscous parts of their naturally viscoelastic substrates modifying their internal structures and nuclear envelope (Discher et al 2017).…”