Extracellular Matrix Remodeling and Mechanical Stresses as Modulators of Adipose Tissue Metabolism and Inflammation - The Mechanobiology of Obesity and Related Diseases - page 114

mechanical cues, ranging from ECM stiffness to tensile, shear or compressive
forces, transduce intracellularly to regulate cell function (Fig. 2 ). Similar to cell-
derived intracellular mechanical forces, the mechanotransduction involves the
RhoA/ROCK pathway, amongst others. These investigations have shed light on
the importance of understanding how bodily movements and physical tissue
interactions play a role in regulating adipose tissue development and formation. In
this regard, there is an exciting opportunity to leverage engineered ECMs and
other advanced bioreactor systems to selectively apply mechanical loads under
tightly controlled microenvironmental conditions. These engineered in vitro cul-
ture systems offer platforms with which to systematically characterize the effects
of specific mechanical forces on adipocytes and their progenitors in isolation from
confounding biochemical influences of the in vivo tissue. Additionally, the ability
to controllably alter the culture substrate (engineered ECM) and medium com-
position should enable studies on the effects of specific combinations of
mechanical and biochemical cues. The possibilities these tools offer range from
elucidating physical effects on adipose tissue in vivo to the engineering of adipose
tissues in vitro. The latter could be used as platforms for research or even
replacement for diseased tissues in vivo.
In closing, we find compelling evidence that mechanical cues arising from cell-
ECM interactions critically influence the biochemical and mechanical properties
of adipose tissue, notably the tissue's plasticity. However, the mechanobiology of
adipose tissue is a relatively new field, and many questions remain regarding the
molecular mechanisms responsible for sensing and transducing mechanical stim-
uli. We expect that the use of engineered adipose tissue systems will help address
these questions by enabling the study of specific mechanical stimuli under well-
defined chemical conditions.

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