Nano-Biomechanical Study of Spatio-Temporal Cytoskeleton Rearrangements that Determine Subcellular Mechanical Properties and Endothelial Permeability.

TitleNano-Biomechanical Study of Spatio-Temporal Cytoskeleton Rearrangements that Determine Subcellular Mechanical Properties and Endothelial Permeability.
Publication TypeJournal Article
Year of Publication2015
AuthorsWang X, Bleher R, Brown ME, Garcia JGN, Dudek SM, Shekhawat GS, Dravid VP
JournalSci Rep
Volume5
Pagination11097
Date Published2015 Jun 18
ISSN Number2045-2322
KeywordsBiomechanical Phenomena, Cells, Cultured, Cytoskeleton, Endothelial Cells, Humans, Mechanical Phenomena, Microscopy, Atomic Force, Microscopy, Fluorescence, Nanotechnology, Permeability
Abstract

<p>The endothelial cell (EC) lining of the pulmonary vascular system forms a semipermeable barrier between blood and the interstitium and regulates various critical biochemical functions. Collectively, it represents a prototypical biomechanical system, where the complex hierarchical architecture, from the molecular scale to the cellular and tissue level, has an intimate and intricate relationship with its biological functions. We investigated the mechanical properties of human pulmonary artery endothelial cells (ECs) using atomic force microscopy (AFM). Concurrently, the wider distribution and finer details of the cytoskeletal nano-structure were examined using fluorescence microscopy (FM) and scanning transmission electron microscopy (STEM), respectively. These correlative measurements were conducted in response to the EC barrier-disrupting agent, thrombin, and barrier-enhancing agent, sphingosine 1-phosphate (S1P). Our new findings and analysis directly link the spatio-temporal complexities of cell re-modeling and cytoskeletal mechanical properties alteration. This work provides novel insights into the biomechanical function of the endothelial barrier and suggests similar opportunities for understanding the form-function relationship in other biomechanical subsystems.</p>

DOI10.1038/srep11097
Alternate JournalSci Rep
PubMed ID26086333
PubMed Central IDPMC4650616
Grant ListP01 HL58064 / HL / NHLBI NIH HHS / United States
R01 HL88144 / HL / NHLBI NIH HHS / United States
P01 HL098050 / HL / NHLBI NIH HHS / United States
P01 HL058064 / HL / NHLBI NIH HHS / United States
R01 HL091889 / HL / NHLBI NIH HHS / United States