title: Nanoparticle Density: A Critical Biophysical Regulator of Endothelial Permeability.
abstract: The integrity of the vasculature system is intrinsically sensitive to a short list of biophysical cues spanning from nano to micro scales. We have earlier found that certain nanomaterials could induce endothelial leakiness (nanoparticle induced endothelial leakiness, nanoEL). In this study, we report that the density of the nanomaterial, a basic intrinsic material property not implicated in many nanoparticle-mediated biological effects, predominantly dictates the nanoEL effect. We demonstrated that the impinging force exerted by a library of increasing effective densities but consistently sized silica nanoparticles (SiNPs) could directly increase endothelial permeability. The crossover effective particle density that induced nanoEL was determined to be between 1.57 g/cm3to 1.72 g/cm3. It was also found that a cumulative gravitational-mediated force of around 1.8 nN/μm along the boundaries of the vascular endothelial cadherin (VE-cad) adherens junctions appeared to be a critical threshold force required to perturb endothelial cell-cell adhesion. The net result is the "snapping" of the mechanically pretensed VE-cad (Nanosnap), leading to the formation of micron-sized gaps that would dramatically increase endothelial leakiness.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , N4.1, 50 Nanyang Avenue, Singapore 639798, Singapore.|School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Chor Yong
authors.initials: CY
authors.lastname: Tay
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Magdiel Inggrid
authors.initials: MI
authors.lastname: Setyawati
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: David Tai
authors.identifier: 0000-0001-8539-9062
authors.initials: DT
authors.lastname: Leong
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D010539:Permeability; D012822:Silicon Dioxide / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D012822:Silicon Dioxide
keywords: VE-cadherin mechanics; biophysics; endothelial cells; nanobio interactions; nanoparticles; particokinetics