Biomedical Engineering Reference
In-Depth Information
The combination of structural proteins interwoven with proteo-
glycans also provides cells with a local and a global mechanical
environment. Variations in composition and architecture determine
their stiffness, measured variously as elasticity, viscoelasticity, or
poroelasticity. 47 Central corneal tissue has a stiffness of 8.6 MPa
and is able to distribute applied loads with great precision in order
to remain nearly perfectly spherical and aberration free, 48 while
liver tissue has a stiffness of 500 Pa. 49 Thus it is clear that cells
require specific stiffness cues in order to maintain proper physio-
logical functions and that their stiffness-sensing mechanisms allow
themtopromoteorinhibitcellularfunctionsaccordingly.Thisisfur-
ther demonstrated in the changes that occur in cells in response to
changes in tissue stiffness, resulting in a remodeling of the tissue.
Takinglivertissueasanexample,hepaticstellatecells(HSCs),which
are activated during tissue injury, produce collagen type I, which in
turncausestheHSCmicroenvironmenttoincreaseinstiffness,exac-
erbating the injury response. 50 On a larger scale, the stiffness of the
organs is directly related to matrix and cellular organization at the
microscale. The skin is an example of thin, organized sheets that
are strong in biaxial tension 51 ; cylindrical blood vessels can resist
circumferential tension 52 ; lung structure and the ability to toler-
ate complex physical forces, including expansive pressures and pul-
monarybloodflow,isattributedtotheconnectivetissuenetwork 53 ;
wideintercellularspacesofintestinalepitheliuminthevilliactcount
for the balance between outward interstitial pressure and inward
muscle pull. 54
By virtue of their location lining internal cavities and lumen,
epithelialtissuesaresubjectedtoshearstressesresultingfromfluid
flow. Atheroprotective shear stresses experienced by endothelial
cells in healthy arteries is
15 dyne/cm 2 , whereas atherosclerotic
arteries experience a lower shear stress of
>
4dyne/cm 2 which
results in modification of endothelial gene expression and pheno-
type, exacerbating the problem. 55
Interstitialflowisalsopresentinepithelialtissues.Thisisdueto
the existence of vasculature within tissues, which sets up flows on
the order of 0.1-1 μ m/s. 56 External stresses exerted on tissues also
contribute to this effect, even though the stresses are temporary. 57
The fluidics of the tissue play an important part in establishing
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