Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-22T17:27:19.171Z Has data issue: false hasContentIssue false
  • English
  • Français

Adipocytes Migration is Altered Through Differentiation

Published online by Cambridge University Press:  30 July 2019

Maayan Lustig Open the ORCID record for Maayan Lustig [Opens in a new window] ,
Yuliya Zadka ,
Irena Levitsky ,
Amit Gefen  and
Dafna Benayahu
Maayan Lustig
Affiliation:
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
Yuliya Zadka
Affiliation:
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
Irena Levitsky
Affiliation:
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
Amit Gefen
Affiliation:
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
Dafna Benayahu*
Affiliation:
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
*
*Author for correspondence: Dafna Benayahu, E-mail: [email protected]
Get access

Abstract

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.

Keywords

adipogenesisdifferentiationholographic-microscopylive-imagingmotility
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 25 , Issue 5 , October 2019 , pp. 1195 - 1200
Copyright
Copyright © Microscopy Society of America 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abuhattum, S, Gefen, A & Weihs, D (2015). Ratio of total traction force to projected cell area is preserved in differentiating adipocytes. Integr Biol 7, 1212–1217.Google Scholar
Abuhattum, S & Weihs, D (2016). Asymmetry in traction forces produced by migrating preadipocytes is bounded to 33%. Med Eng Phys 38, 834–838.Google Scholar
Ali, AT, Hochfeld, WE, Myburgh, R & Pepper, MS (2013). Adipocyte and adipogenesis. Eur J Cell Biol 92, 229–236.Google Scholar
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, 247–254.Google Scholar
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, 15–28.Google Scholar
Cai, Y & Sheetz, MP (2009). Force propagation across cells: Mechanical coherence of dynamic cytoskeletons. Curr Opin Cell Biol 21, 47–50.Google Scholar
Cooper, JA & Schafer, DA (1995). Control of actin assembly at filament ends. Annu Rev Cell Dev Biol 11, 497–518.Google Scholar
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, 2609–2614.Google Scholar
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.Google Scholar
Fletcher, DA & Mullins, RD (2010). Cell mechanics and the cytoskeleton. Nature 463, 485–492.Google Scholar
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, 131–141.Google Scholar
Geiger, B, Spatz, JP & Bershadsky, AD (2009). Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10, 21–33.Google Scholar
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, 1–6.Google Scholar
Gumbiner, BM (1996). Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 84, 345–357.Google Scholar
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, 553–563.Google Scholar
Huttenlocher, A & Horwitz, AR (2011). Integrins in cell migration. Cold Spring Harbor Perspect Biol 3, a005074.Google Scholar
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, 910–919.Google Scholar
Katzengold, R, Shoham, N, Benayahu, D & Gefen, A (2015). Simulating single cell experiments in mechanical testing of adipocytes. Biomech Model Mechanobiol 14, 537–547.Google Scholar
Kaverina, I, Krylyshkina, O & Small, JV (2002). Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 34, 746–761.Google Scholar
Khalili, AA & Ahmad, MR (2015). A review of cell adhesion studies for biomedical and biological applications. Int J Mol Sci 16, 18149–18184.Google Scholar
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, 125–130.Google Scholar
Kim, MK (2010). Principles and techniques of digital holographic microscopy. SPIE Rev 1, 018005.Google Scholar
Lauffenburger, DA & Horwitz, AF (1996). Cell migration: A physically integrated molecular process. Cell 84, 359–369.Google Scholar
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, 1052–1060.Google Scholar
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, 119–128.Google Scholar
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, 903–913.Google Scholar
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. 171–174. Cham: Springer.Google Scholar
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, 483–495.Google Scholar
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, 3850–3863.Google Scholar
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, 171–180.Google Scholar
Parsons, JT, Horwitz, AR & Schwartz, MA (2010). Cell adhesion: Integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol 11, 633–643.Google Scholar
Pelham, RJ & Wang, YL (1997). Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci 94, 13661–13665.Google Scholar
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.Google Scholar
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, 1704–1709.Google Scholar
Rosen, ED & Macdougald, OA (2006). Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7, 885–896.Google Scholar
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.Google Scholar
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, 2637–2653.Google Scholar
Shoham, N & Gefen, A (2012 a). Mechanotransduction in adipocytes. J Biomech 45, 1–8.Google Scholar
Shoham, N & Gefen, A (2012 b). The influence of mechanical stretching on mitosis, growth, and adipose conversion in adipocyte cultures. Biomech Model Mechanobiol 11, 1029–1045.Google Scholar
Shoham, N, Girshovitz, P, Katzengold, R, Shaked, NT, Benayahu, D & Gefen, A (2014). Adipocyte stiffness increases with accumulation of lipid droplets. Biophys J 106, 1421–1431.Google Scholar
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, C429–C441.Google Scholar
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, 1–21.Google Scholar
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, 1354–1363.Google Scholar
Siegel, AL, Atchison, K, Fisher, KE, Davis, GE & Cornelison, DDW (2009). 3D timelapse analysis of muscle satellite cell motility. Stem Cells 27, 2527–2538.Google Scholar
Spiegelman, BM & Farmer, SR (1982). Decreases in tubulin and actin gene expression prior to morphological differentiation of 3T3 adipocytes. Cell 29, 53–60.Google Scholar
Spiegelman, BM & Flier, JS (1996). Adipogenesis and obesity: Rounding out the big picture. Cell 87, 377–389.Google Scholar
Spiegelman, BM & Ginty, CA (1983). Fibronectin modulation of cell shape and lipogenic gene expression in 3t3-adipocytes. Cell 35, 657–666.Google Scholar
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, 251–261.Google Scholar
Wang, N, Butler, J & Ingber, D (1993). Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127.Google Scholar
Wozniak, MA, Modzelewska, K, Kwong, L & Keely, PJ (2004). Focal adhesion regulation of cell behavior. Biochim Biophys Acta (BBA)—Mol Cell Res 1692, 103–119.Google Scholar
Yamazaki, D, Kurisu, S & Takenawa, T (2009). Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 28, 1570–1583.Google Scholar
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, 8581–8588.Google Scholar