Skip to main content Accessibility help

Adipocytes Migration is Altered Through Differentiation

  • Maayan Lustig (a1), Yuliya Zadka (a1), Irena Levitsky (a1), Amit Gefen (a1) and Dafna Benayahu (a2)...


Adipogenesis is a developmental process in which an elongated preadipocyte differentiates to a round adipocyte along with the accumulation of lipid droplets. In the present study, we focus on the study of cell motility at the single-cell level, toward expanding our knowledge regarding the cytoskeleton alteration during differentiation; since-cell motility is mediated by cytoskeletal components. We used the holographic-microscopy live imaging technique to evaluate, for the first time in the literature, differences between the motility of nondifferentiated preadipocytes and differentiated mature adipocytes in living cell cultures over time. We revealed that mean motility speed of preadipocytes was significantly higher (fourfold) than that of adipocytes, and that the movement of preadipocytes is less consistent and more extensive. Furthermore, we found that preadipocytes tend to migrate to farther distances, while mature adipocytes remain relatively close to their original location. The results presented here are in agreement with the fact that the cytoskeleton of adipocytes is altered during differentiation and similarly, points to the fact that the cell-sensing mechanisms are changing during differentiation. Our research paves the way to gain better insights of the differentiation process and its implications on larger scale systems in the context of obesity.


Corresponding author

*Author for correspondence: Dafna Benayahu, E-mail:


Hide All
Abuhattum, S, Gefen, A & Weihs, D (2015). Ratio of total traction force to projected cell area is preserved in differentiating adipocytes. Integr Biol 7, 12121217.
Abuhattum, S & Weihs, D (2016). Asymmetry in traction forces produced by migrating preadipocytes is bounded to 33%. Med Eng Phys 38, 834838.
Ali, AT, Hochfeld, WE, Myburgh, R & Pepper, MS (2013). Adipocyte and adipogenesis. Eur J Cell Biol 92, 229236.
Antras, J, Hilliou, F, Redziniak, G & Pairault, J (1989). Decreased biosynthesis of actin and cellular fibronectin during adipose conversion of 3T3-F442A cells. Reorganization of the cytoarchitecture and extracellular matrix fibronectin. Biol Cell 66, 247254.
Ben-Or Frank, M, Shoham, N, Benayahu, D & Gefen, A (2015). Effects of accumulation of lipid droplets on load transfer between and within adipocytes. Biomech Model Mechanobiol 14, 1528.
Cai, Y & Sheetz, MP (2009). Force propagation across cells: Mechanical coherence of dynamic cytoskeletons. Curr Opin Cell Biol 21, 4750.
Cooper, JA & Schafer, DA (1995). Control of actin assembly at filament ends. Annu Rev Cell Dev Biol 11, 497518.
Crandall, DL, Busler, DE, McHendry-Rinde, B, Groeling, TM & Kral, JG (2000). Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1. J Clin Endocrinol Metab 85, 26092614.
Feng, Y, Zhu, M, Dangelmajer, S, Lee, YM, Wijesekera, O, Castellanos, CX, Denduluri, A, Chaichana, KL, Li, Q, Zhang, H, Levchenko, A, Guerrero-Cazares, H & Quiñones-Hinojosa, A (2014). Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer. Cell Death Dis 5, e1567.
Fletcher, DA & Mullins, RD (2010). Cell mechanics and the cytoskeleton. Nature 463, 485492.
Franke, WW, Hergt, M & Grund, C (1987). Rearrangement of the vimentin cytoskeleton during adipose conversion: Formation of an intermediate filament cage around lipid globules. Cell 49, 131141.
Geiger, B, Spatz, JP & Bershadsky, AD (2009). Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10, 2133.
Glait-Santar, C & Benayahu, D (2013) Insights into cell adhesion molecules with a focus on bone as a favorable site for tumor growth. Trends Cell Mol Biol 8, 16.
Gumbiner, BM (1996). Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 84, 345357.
Gustafsson, M, Sebesta, M, Bengtsson, B, Pettersson, SG, Egelberg, P & Lenart, T (2004). High-resolution digital transmission microscopy—a Fourier holography approach. Opt Lasers Eng 41, 553563.
Huttenlocher, A & Horwitz, AR (2011). Integrins in cell migration. Cold Spring Harbor Perspect Biol 3, a005074.
Kapałczyńska, M, Kolenda, T, Przybyła, W, Zajączkowska, M, Teresiak, A, Filas, V, Ibbs, M, Bliźniak, R, Łuczewski, Ł & Lamperska, K (2018). 2D and 3D cell cultures––a comparison of different types of cancer cell cultures. Arch Med Sci: AMS 14, 910919.
Katzengold, R, Shoham, N, Benayahu, D & Gefen, A (2015). Simulating single cell experiments in mechanical testing of adipocytes. Biomech Model Mechanobiol 14, 537547.
Kaverina, I, Krylyshkina, O & Small, JV (2002). Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 34, 746761.
Khalili, AA & Ahmad, MR (2015). A review of cell adhesion studies for biomedical and biological applications. Int J Mol Sci 16, 1814918184.
Kim, CS, Kawada, T, Yoo, H, Kwon, BS & Yu, R (2003). Macrophage inflammatory protein-related protein-2, a novel CC chemokine, can regulate preadipocyte migration and adipocyte differentiation. FEBS Lett 548, 125130.
Kim, MK (2010). Principles and techniques of digital holographic microscopy. SPIE Rev 1, 018005.
Lauffenburger, DA & Horwitz, AF (1996). Cell migration: A physically integrated molecular process. Cell 84, 359369.
Levy, A, Enzer, S, Shoham, N, Zaretsky, U & Gefen, A (2012). Large, but not small sustained tensile strains stimulate adipogenesis in culture. Ann Biomed Eng 40, 10521060.
Lustig, M, Feng, Q, Payan, Y, Gefen, A & Benayahu, D (2019). Noninvasive continuous monitoring of adipocyte differentiation: From macro to micro scales. Microsc Microanal 25, 119128.
Lustig, M, Gefen, A & Benayahu, D (2018 a). Adipogenesis and lipid production in adipocytes subjected to sustained tensile deformations and elevated glucose concentration: A living cell-scale model system of diabesity. Biomech Model Mechanobiol 17, 903913.
Lustig, M, Moldovan Mor Yossef, L, Gefen, A & Benayahu, D (2018 b). Adipogenesis of 3T3L1 cells subjected to tensile deformations under various glucose concentrations. In Computer Methods in Biomechanics and Biomedical Engineering, Gefen, A & Weihs, D (Eds.), pp. 171174. Cham: Springer.
Mcbeath, R, Pirone, DM, Nelson, CM, Bhadriraju, K & Chen, CS (2004). Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6, 483495.
Mor-Yossef Moldovan, L, Lustig, M, Naftaly, A, Mardamshina, M, Geiger, T, Gefen, A & Benayahu, D (2019). Cell shape alteration during adipogenesis is associated with coordinated matrix cues. J Cell Physiol 234, 38503863.
Omatsu-Kanbe, M, Inoue, K, Fujii, Y, Yamamoto, T, Isono, T, Fujita, N & Matsuura, H (2006). Effect of ATP on preadipocyte migration and adipocyte differentiation by activating P2Y receptors in 3T3-L1 cells. Biochem J 393, 171180.
Parsons, JT, Horwitz, AR & Schwartz, MA (2010). Cell adhesion: Integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol 11, 633643.
Pelham, RJ & Wang, YL (1997). Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci 94, 1366113665.
Phase Holographic Imaging PHI AB (2018). HoloMonitor M4 setup and operation manual. Hstudio 2.7.3, rev. 8, Phase Holographic Imaging PHI AB, Scheelevägen, Lund, Sweden.
Ridley, AJ, Schwartz, MA, Burridge, K, Firtel, RA, Ginsberg, MH, Borisy, G, Parsons, JT & Horwitz, AR (2003). Cell migration: Integrating signals from front to back. Science 302, 17041709.
Rosen, ED & Macdougald, OA (2006). Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7, 885896.
Sebesta, M, Egelberg, PJPJ, Langberg, A, Lindskov, J-H, Alm, K & Janicke, B (2016). Holomonitor M4: Holographic imaging cytometer for real-time kinetic label-free live-cell analysis of adherent cells. Progr Biomed Opt Imag—Proc SPIE 9718, 971813.
Shoham, N & Gefen, A (2011). Stochastic modeling of adipogenesis in 3T3-L1 cultures to determine probabilities of events in the cell's life cycle. Ann Biomed Eng 39, 26372653.
Shoham, N & Gefen, A (2012 a). Mechanotransduction in adipocytes. J Biomech 45, 18.
Shoham, N & Gefen, A (2012 b). The influence of mechanical stretching on mitosis, growth, and adipose conversion in adipocyte cultures. Biomech Model Mechanobiol 11, 10291045.
Shoham, N, Girshovitz, P, Katzengold, R, Shaked, NT, Benayahu, D & Gefen, A (2014). Adipocyte stiffness increases with accumulation of lipid droplets. Biophys J 106, 14211431.
Shoham, N, Gottlieb, R, Sharabani-Yosef, O, Zaretsky, U, Benayahu, D & Gefen, A (2012). Static mechanical stretching accelerates lipid production in 3T3-L1 adipocytes by activating the MEK signaling pathway. AJP: Cell Physiol 302, C429C441.
Shoham, N, Levy, A, Shabshin, N, Benayahu, D & Gefen, A (2016). A multiscale modeling framework for studying the mechanobiology of sarcopenic obesity. Biomech Model Mechanobiol 16, 121.
Shoham, N, Mor-Yossef Moldovan, L, Benayahu, D & Gefen, A (2015). Multiscale modeling of tissue-engineered fat: Is there a deformation-driven positive feedback loop in adipogenesis? Tissue Eng, Part A 21, 13541363.
Siegel, AL, Atchison, K, Fisher, KE, Davis, GE & Cornelison, DDW (2009). 3D timelapse analysis of muscle satellite cell motility. Stem Cells 27, 25272538.
Spiegelman, BM & Farmer, SR (1982). Decreases in tubulin and actin gene expression prior to morphological differentiation of 3T3 adipocytes. Cell 29, 5360.
Spiegelman, BM & Flier, JS (1996). Adipogenesis and obesity: Rounding out the big picture. Cell 87, 377389.
Spiegelman, BM & Ginty, CA (1983). Fibronectin modulation of cell shape and lipogenic gene expression in 3t3-adipocytes. Cell 35, 657666.
Verstraeten, VLRM, Renes, J, Ramaekers, FCS, Kamps, M, Kuijpers, HJ, Verheyen, F, Wabitsch, M, Steijlen, PM, Van Steensel, MAM & Broers, JLV (2011). Reorganization of the nuclear lamina and cytoskeleton in adipogenesis. Histochem Cell Biol 135, 251261.
Wang, N, Butler, J & Ingber, D (1993). Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 11241127.
Wozniak, MA, Modzelewska, K, Kwong, L & Keely, PJ (2004). Focal adhesion regulation of cell behavior. Biochim Biophys Acta (BBA)—Mol Cell Res 1692, 103119.
Yamazaki, D, Kurisu, S & Takenawa, T (2009). Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 28, 15701583.
Young, DA, Choi, YS, Engler, AJ & Christman, KL (2013). Stimulation of adipogenesis of adult adipose-derived stem cells using substrates that mimic the stiffness of adipose tissue. Biomaterials 34, 85818588.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed