title: Cellular cholesterol regulates monocyte deformation.
abstract: 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 deformability, 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.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX, United States.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Saha
authors.affiliation: Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX, United States.
authors.forename: Shatha F
authors.initials: SF
authors.lastname: Dallo
authors.affiliation: Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX, United States.
authors.forename: Ariana L
authors.initials: AL
authors.lastname: Detmar
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
authors.forename: Pawel
authors.initials: P
authors.lastname: Osmulski
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Gaczynska
authors.affiliation: Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
authors.forename: Tim Hui-Ming
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Biomedical, Chemical and Materials Engineering, San José State University, San José, CA, United States. Electronic address: anand.ramasubramanian@sjsu.edu.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ramasubramanian
mesh_terms: D001696:Biomechanical Phenomena; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D055595:Mechanical Phenomena; D008560:Membrane Fluidity; D009000:Monocytes / Q000166:cytology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D002784:Cholesterol; D011493:Protein Kinase C
keywords: Cell deformability; Cell stiffness; Cytoskeleton; Membrane fluidity; Microfluidics; Spreading