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SUMMARY:The mechanobiology of adipocytes - Gefen\, A (Tel Aviv University)
DTSTART:20151103T100000Z
DTEND:20151103T110000Z
UID:TALK62239@talks.cam.ac.uk
CONTACT:42080
DESCRIPTION:We recently discovered that fat cells (adipocytes) are mechano
 sensitive and responsive to sustained mechanical loading. This discovery i
 s fundamentally important for understanding the long-term effects of a sed
 entary life style (i.e. prolonged sitting and lying periods)\, given that 
 such a lifestyle predominantly involves static mechanical loads acting upo
 n and within the cells. Our cell-level biomechanical research approach rev
 ealed accelerated adipogenesis (production of triglycerides) in cells subj
 ected to sustained large deformations. Specifically\, we have developed ti
 ssue-engineered three-dimensional (3D) fat cultures in order to determine 
 their mechanical behavior under large physiological deformations. We have 
 further investigated the mechanical behavior of maturing adipocytes in vit
 ro and in silico\, to understand the biomechanical cell-cell interactions 
 that potentially lead to increase in adipogenesis and eventually\, gain of
  additional fat mass. We showed how these cell-cell biomechanical interact
 ions trigger molecular signaling pathways such as the MAPK/ERK\, which act
 ivate the adipogenesis. Additional novel findings from our group\, at the 
 individual adipocyte cell-level\, demonstrated an increase in cell stiffne
 ss with accumulation of intra-cytoplasmic lipid droplets (LDs) using both 
 atomic force and interferometric phase microscopies. These results were us
 ed together to develop 3D computational finite element cell modeling of ad
 ipocytes\, for simulating the structural\, large deformation behavior of t
 he maturing adipocytes. Based on our modeling framework\, we found that ex
 ternal loads induced localized large strains in the plasma membrane of the
  cells\, which had maximum values over the LDs\, thereby providing an expl
 anation regarding how mechanical stimulation accelerated the adipogenesis.
  The above experimental model systems of cultured adipocytes that were dev
 eloped in our laboratory facilitated development of multi-scale in silico 
 models of adipocytes embedded in an extracellular matrix. These computatio
 nal models provided the first evidence that sustained deformations in weig
 ht-bearing adipose tissues\, as in a sedentary lifestyle\, can indeed acti
 vate a vicious cycle that takes the form of a positive feedback loop promo
 ting "en mass" adipogenesis. This leads to a viscous cycle at the tissue-s
 cale\, which eventually increases the total mass of fat tissues. Our publi
 shed studies overall provide the explanation regarding how maturing adipoc
 ytes deform each other in weight-bearing fat tissues\, in a spiral that co
 ntributes to the adipogenesis at the cell-scale\, and then to gain of fat 
 mass\, overweight and obesity at the tissue and body scales.\n
LOCATION:Seminar Room 2\, Newton Institute Gatehouse
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