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Tensional homeostasis in single fibroblasts
#MMPMID24988349
Webster KD
; Ng WP
; Fletcher DA
Biophys J
2014[Jul]; 107
(1
): 146-55
PMID24988349
show ga
Adherent cells generate forces through acto-myosin contraction to move, change
shape, and sense the mechanical properties of their environment. They are thought
to maintain defined levels of tension with their surroundings despite mechanical
perturbations that could change tension, a concept known as tensional
homeostasis. Misregulation of tensional homeostasis has been proposed to drive
disorganization of tissues and promote progression of diseases such as cancer.
However, whether tensional homeostasis operates at the single cell level is
unclear. Here, we directly test the ability of single fibroblast cells to
regulate tension when subjected to mechanical displacements in the absence of
changes to spread area or substrate elasticity. We use a feedback-controlled
atomic force microscope to measure and modulate forces and displacements of
individual contracting cells as they spread on a fibronectin-patterned
atomic-force microscope cantilever and coverslip. We find that the cells reach a
steady-state contraction force and height that is insensitive to stiffness
changes as they fill the micropatterned areas. Rather than maintaining a constant
tension, the fibroblasts altered their contraction force in response to
mechanical displacement in a strain-rate-dependent manner, leading to a new and
stable steady-state force and height. This response is influenced by
overexpression of the actin crosslinker ?-actinin, and rheology measurements
reveal that changes in cell elasticity are also strain- rate-dependent. Our
finding of tensional buffering, rather than homeostasis, allows cells to
transition between different tensional states depending on how they are
displaced, permitting distinct responses to slow deformations during tissue
growth and rapid deformations associated with injury.
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