Contributions of the active and passive components of the cytoskeletalprestress to stiffening of airway smooth muscle cells.
Rosenblatt,N; Hu,S; Suki,B; Wang,N; Stamenovic,D
Abstract Airway smooth muscle cells exhibit stiffening during contractile activation.This stiffening may be interpreted as a result of the stabilizing influence of the mechanicalprestress stored within the cytoskeleton (CSK). However, in vivo, airway smooth muscle cellscontract while simultaneously experiencing breathing-induced stretching. Excessive stretching ofcells could cause actin-myosin crosslinks, and possibly other cytoskeletal filaments, to break,thereby leading to dissipation of the prestress and inhibition of further cell stiffening. The aimof this study is to investigate the stiffening behavior of individual human airway smooth muscle(HASM) cells exposed to a combination of substrate stretching, contractile activation andrelaxation. We treated cultured HASM cells with either contractile (histamine) or relaxing (DBcAMP)pharmacological agonists and used magnetic cytometry technique to investigate the stiffeningbehavior of these cells during uniform substrate stretching (0-30%). Cells that were not treated, aswell as those treated with histamine, exhibited increasing stiffening during stretching up to 20%of substrate strain, with additional stiffening becoming inhibited for substrate strains of 20-30%.In contrast, in cells treated with DBcAMP, stretching produced moderate but continuous stiffeningwith increasing substrate strain. These results indicate that both active and passive components ofthe prestress contribute to cell stiffening. We also observed that cells permeabilized with saponinexhibited stiffening at low levels (<10%) of substrate stretching, similar to non-permeabilizedcells, but not at high levels (10-30%) of stretching, where stiffening was inhibited. These datasuggest that at low levels of substrate strains the relative contributions of ion channel activationas well as actin and focal adhesion remodeling are less important for stiffening than passivedistension of the CSK. Taken together, our results suggest that both the active and passivecomponents of the cytoskeletal prestress contribute to the stiffening behavior of HASM cells underphysiological conditions, but that at high levels of cellular distensions there is a possibletradeoff between these two components with the contribution from the passive component becomingincreasingly more important.
Keywords Cytoskeleton; Larynx; Mechanotransduction, Cellular; Models, Biological
Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-234
