Effects of serum deprivation on the mechanical properties of adherent vascular smooth muscle cells

Abstract

Vascular smooth muscle cell (VSMC) function plays a key role in regulating the development and progression of vascular lesions. Among the more significant phenomena that occur during the development of these lesions is the phenotypic switching of VSMCs from a contractile to a synthetic state. A better understanding of the concurrent changes to VSMC mechanical properties that occur with phenotypic shifts can help to elucidate the role of VSMC mechanics in the development of vascular diseases. In the current study, the mechanical properties of adherent cultured rat aortic VSMCs were assessed by atomic force microscopy. Serum starvation was used to induce a phenotypic shift in vitro. It was concluded that serum starvation led to a statistically significant increase in apparent elastic modulus after 5 days, as well as a statistically significant decrease in hysteresis after culture for 3 days. If this trend of VSMC mechanical properties changing concurrently with phenotypic shifts were to hold true in vivo, such changes could affect the processes of mechanotransduction and/or arterial mechanical properties, thereby contributing to the progression of vascular disease.

Altered phenotypic gene expression of 10T1/2 mesenchymal cells in nonuniformly stretched PEGDA hydrogels

“…However, in that case the stiffness mismatch of materials was a factor of 10 (i.e., mechanical stiffness properties of calcifications were 10 times greater than those of the surrounding fibrin cap). Within our gels, the mismatch of cell and hydrogel stiffnesses is probably not as drastic, as evidenced by previous mechanical characterizations (7,19,36). Browning et al (7) uniaxially strained PEGDA hydrogel rings and calculated a secant modulus of stress-strain data, which yielded a value of 19 kPa for 20% concentration, 10-kDa molecular mass gels as used here.…”

“…Browning et al (7) uniaxially strained PEGDA hydrogel rings and calculated a secant modulus of stress-strain data, which yielded a value of 19 kPa for 20% concentration, 10-kDa molecular mass gels as used here. The apparent elastic moduli of rat aortic SMCs and murine embryonic cells have been measured by atomic force microscopy (AFM) indentation in the respective ranges of 10 -25 kPa and 0.5-16 kPa, depending on level of serum deprivation or differentiation state (19,36). Thus, in our case, although the stiffnesses of 10T1/2 cells and PEGDA hydrogels are certainly not identical, they are probably within the same order of magnitude.…”

Contractility Dominates Adhesive Ligand Density in Regulating Cellular De-adhesion and Retraction Kinetics

“…In that study, cell stiffness by AFM did not change significantly in the setting of serum starvation, which the authors attributed to compensatory compaction of intermediate filaments around the nucleus. In fact, Hemmer et al 9. reported that serum starvation increases the AFM-measured stiffness of vascular smooth muscle cells, which they suggested may be secondary to serum-induced changes in shape and spreading area.…”

The effect of the serum corona on interactions between a single nano-object and a living cell

“…As the modulus is an internal cellular property that depends largely on the cytoskeleton structure, it should not be affected by tip coating such as the serum protein corona. As all cells were cultured under identical conditions, those incubated in serum and those without serum during the measurements should have the same overall modulus; indeed, it has been shown49 that the presence or absence or serum proteins does not affect the overall cell modulus over periods shorter than 3 days. We thus extracted the effective modulus E* = 1.3 kPa of our cells from the Group I results as noted above, and attempted to use this value for fitting the data of group II, as it appears in Fig.…”