Cellular cholesterol regulates monocyte deformation

JOURNAL OF BIOMECHANICS

卷:52

Article

Saha, Amit K.¹  Dallo, Shatha F.¹  Detmar, Ariana L.¹  Osmulski, Pawel²  Gaczynska, Maria²  Huang, Tim Hui-Ming²  Ramasubramanian, Anand K.³ 

[1] Univ Texas San Antonio, Dept Biomed Engn, San Antonio, DC USA

[2] Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX USA

[3] San Jose State Univ, Dept Biomed Chem & Mat Engn, San Jose, CA USA

关键词: Microfluidics;    Cytoskeleton;    Cell deformability;    Spreading;    Membrane fluidity;    Cell stiffness;   

DOI  :  10.1016/j.jbiomech.2016.12.033

来源: Elsevier

【 摘 要 】

The role of cholesterol content on monocyte biomechanics remains understudied despite the well established link between cholesterol and monocytes/macrophages in atherosclerosis, and the effect on other cell types. In this work, we have investigated the effect of cholesterol on monocyte deformability and the underlying molecular mechanisms. We altered the baseline cholesterol in human monocytic cell line THP-1, and investigated the changes in monocyte deformability using a custom microfluidic platform and atomic force microscopy. We observed that the cholesterol depletion lowered deformability while enrichment increased deformability compared to untreated cells. As a consequence of altered deform ability, cholesterol depleted cells spread more on collagen-coated surfaces with elongated morphology, whereas cholesterol enriched cells had a more rounded morphology. We observed that the decreased deformability in cholesterol depleted cells, despite an increase in the fluidity of the membrane, is due to an increase in phosphorylation of Protein Kinase C (PKC), which translates to a higher degree of actin polymerization. Together, our results highlight the importance of biophysical regulation of monocyte response to cholesterol levels. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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