Figure 8
From: Actin cap associated focal adhesions and their distinct role in cellular mechanosensing
The unique response of actin cap and actin cap associated focal adhesions in response to substrate compliance.
(A) Schematic of the cellular mechanosensing in response to substrate compliance. Well-organized actin cap fibers (green) on top of the nucleus are terminated by ACAFAs (red) at the pheriphery of the adherent cell and nucleus (blue) is elongated in the same direction as actin cap fibers (Left). As substrate compliance increases, ACAFAs and actin cap fibers disappear, but CFAs (yellow) and basal actin fibers (black) remain and the nucleus becomes rounded (Middle). On extremely soft substrates, most actin stress fibers and focal adhesions disassemble and the nucleus is more rounded (Right). Inset. Physical connections between actin cap stress fibers and nucleus through the linker of nucleoskeleton and cytoskeleton (LINC) complexes. PNS: perinuclear space; INM: inner nuclear membrane; ONM: outer nuclear membrane. By disrupting LINC complexes, actin cap fibers become disorganized and mechanosensing controlled by actin cap associated focal adhesions is suppressed. (B) and (C) The extremely wide range of substrate stiffness for which only ACAFAs respond (B). Tissue elasticity data adapted from Buxboim et al.38. Response of the size of focal adhesions to substrate stiffness changes (C). Data adapted from Figure 5E was replotted. ***: P < 0.001; NS: P > 0.05. (D) Schematic of the conversion of ACAFAs from CFAs. Dynamic movements of the nucleus induce conventional focal adhesions to turn into actin cap associated focal adhesions, which is accompanied by increases in pFAK, vinculin and p-MLC2 contents and an increase in the size of focal adhesions. Vice versa, actin cap associated focal adhesions can turn into conventional focal adhesions as actin cap fibers turn into basal stress (see also Fig. S10 and Suppl. movie 3).
