Adipocyte Stiffness Increases with Accumulation of Lipid Droplets

Abstract

Adipogenesis and increase in fat tissue mass are mechanosensitive processes and hence should be influenced by the mechanical properties of adipocytes. We evaluated subcellular effective stiffnesses of adipocytes using atomic force microscopy (AFM) and interferometric phase microscopy (IPM), and we verified the empirical results using finite element (FE) simulations. In the AFM studies, we found that the mean ratio of stiffnesses of the lipid droplets (LDs) over the nucleus was 0.83 ± 0.14, from which we further evaluated the ratios of LDs over cytoplasm stiffness, as being in the range of 2.5 to 8.3. These stiffness ratios, indicating that LDs are stiffer than cytoplasm, were verified by means of FE modeling, which simulated the AFM experiments, and provided good agreement between empirical and model-predicted structural behavior. In the IPM studies, we found that LDs mechanically distort their intracellular environment, which again indicated that LDs are mechanically stiffer than the surrounding cytoplasm. Combining these empirical and simulation data together, we provide in this study evidence that adipocytes stiffen with differentiation as a result of accumulation of LDs. Our results are relevant to research of adipose-related diseases, particularly overweight and obesity, from a mechanobiology and cellular mechanics perspectives.

Optical assessment of changes in mechanical and chemical properties of adipose tissue in diet‐induced obese rats

“…Additionally, while the stiffness of AT of the control group varied slightly from animal to animal, the BAT generally possessed a lower Brillouin shift than the WAT. Elasticity measurements in studies of obesity’s effect on adipose [10,18] and lipid accumulation’s effect on adipocytes [6] indirectly support our findings. The Raman spectra were used to estimate the protein to lipid ratio in the sampled location, and the results indicate that the amount of lipids increases greatly in the HFD group, as the ratio decreases.…”

“…The observed increase in the stiffness of both BAT and WAT between control and HFD groups is then most likely the result of adipocyte enlargement and greater crosslinking of collagen fibers, both of which are present in obesity and correlated to an increase in stiffness. [6,8]…”

“…On microscopic level, the mechanical properties of adipocytes are largely determined by the number, size, and content of their lipid droplets. [6] On the macroscopic level the stiffness of the AT is determined by the ECM and cellular composition of the tissue (including type, size and distribution of cells). [4,7] Adipocytes are mechanosensitive and mechanoresponsive cells whose differentiation and function are affected by the applied stress and mechanical properties of their environment, [8,9] which is, in turn, affected by the surrounding adipocytes.…”

Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

“…Considering cells that are also differentiating, the structural organization of the cell changes over time, which affects its stiffness and CSK arrangement, and hence its ability to resist deformation or deform to redistribute the loads. For example, in differentiating adipocytes or myoblasts, respectively, lipid droplets and myotubes form, modifying the cells ability to resist load, which has been demonstrated by the Gefen lab, particularly in adipocytes [63][64][65] .…”

Opportunities and challenges in three-dimensional brown adipogenesis of stem cells

“…Interestingly, AFM measurements determined the stiffness ratio of the lipid droplet in 3T3-L1 differentiated adipocytes to the nucleus to be 0.83 ± 0.14 and that of the lipid droplet to the cytoplasm ranging from 2.5–8.3. It indicates that the lipid droplets are stiffer than cytoplasm, and therefore, mechanically distort their intracellular environment (Shoham et al, 2014). …”