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ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

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5. DISCUSSION<br />

The results of our study provide preliminary evidence that it is feasible to quantitatively<br />

map stiffness distribution within differentiating adipocytes, by the non-contact WFDI<br />

technique, where no exogenous labeling or special sample preparations are involved.<br />

Lipid areas in the adipocyte were found to be ~10 times stiffer than the surrounding<br />

cytoplasm. Nevertheless, expanding the number of examined adipocytes as well as<br />

measuring the exact characteristic refractive indexes of the adipocyte cytoplasm and its<br />

lipid droplets are needed in order to improve the accuracy of the results.<br />

Our findings are in agreement with results obtained previously for red blood cells, using<br />

the same WFDI method (Shaked et el., 2011). Stiffness of adipocytes was measured in<br />

only one reported study by means of AFM (Darling et al., 2008), but the measurements<br />

were made before the adipocytes were allowed to adhere to their substrate, which makes<br />

the results non-comparable. Nevertheless, the data provided in our study, can be used in<br />

numerical models for the purpose of determining how effective stiffness of adipoctye is<br />

influenced by the differentiation process (and the accumulation of the additional lipid<br />

droplets). Given that the effective stiffness of adipocytes (and fat tissues) directly<br />

influence on the applied deformation when adipose tissues are weight bearing, such<br />

studies might clarify whether there exists a positive or negative feedback in the<br />

structure-function-adaption loop for fat, that is, whether formation or growth of<br />

intracytoplasmic lipid droplets leads to softening or stiffening of the cells and tissues. If<br />

this process ultimately results in continuum-scale stiffening, the extent of tissue<br />

deformations, in particular their tensional components would eventually plateau, hence<br />

the mechanical driving force for the differentiation would also stabilize, which would<br />

lead to a physiological equilibrium in the tissue. If on the other hand adipocytes (and<br />

adipose tissues) soften as they mature – that would increase deformability at the tissue<br />

scale, would deliver more stretching to pre-adipocytes and promote further<br />

differentiation, in a positive feedback loop which could contribute to obesity or weight<br />

gaining, and eventually to hyperlipidemia as well. These exciting ideas might open<br />

completely new research paths for studying obesity, diabetes and related diseases from a<br />

biomechanical point-of-view, involving the mechanotransduction and structurefunction-adaptation<br />

concepts that are well known to exist for other tissues but were so<br />

far very poorly studied in fat.<br />

8. REFERENCES<br />

1. Flegal K. M., Carroll M. D., Ogden C. L. and Curtin L. R., Prevalence and trends in<br />

obesity among US adults, 1999-2008. JAMA., 2010, Vol. 303, 235-241.<br />

2. Hausman D. B., DiGirolamo M., Bartness T. J., Hausman G. J. and Martin R. J,.<br />

The biology of white adipocyte proliferation. Obes. Rev., 2001, Vol. 2, 239-254.<br />

3. Main M. L., Rao S. C. and O'keefe J. H., Trends in obesity and extreme obesity<br />

among US adults. JAMA., 2010, Vol. 303, 1695-1696.<br />

4. Shoham N. and Gefen A, Mechanotransduction in adipocytes. J. Biomech., 2011a,<br />

Vol. 45, 1-8.<br />

5. Shoham N., Gottlieb R., Sharabani-Yosef O., Zaretsky U., Benayahu D. and Gefen<br />

A., Static mechanical stretching accelerates lipid production in 3T3-L1 adipocytes<br />

by activating the MEK signaling pathway. Am. J. Physiol. Cell Physiol., 2010b, Vol<br />

302, 429-441.<br />

6. Levy A., Enzer S., Shoham N., Zaretsky U. and Gefen A, Large, but not small<br />

5

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