title: Collagen matrix deposition is dramatically enhanced in vitro when crowded with charged macromolecules: the biological relevance of the excluded volume effect.
abstract: The excluded volume effect (EVE) rules all life processes. It is created by macromolecules that occupy a given volume thereby confining other molecules to the remaining space with large consequences on reaction kinetics and molecular assembly. Implementing EVE in fibroblast culture accelerated conversion of procollagen to collagen by procollagen C-proteinase (PCP/BMP-1) and proteolytic modification of its allosteric regulator, PCOLCE1. This led to a 20-30- and 3-6-fold increased collagen deposition in two- and three-dimensional cultures, respectively, and creation of crosslinked collagen footprints beneath cells. Important parameters correlating with accelerated deposition were hydrodynamic radius of macromolecules and their negative charge density.
authors.affiliation: Tissue Modulation Laboratory, Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore.
authors.forename: Ricky R
authors.initials: RR
authors.lastname: Lareu
authors.forename: Karthik Harve
authors.initials: KH
authors.lastname: Subramhanya
authors.forename: Yanxian
authors.initials: Y
authors.lastname: Peng
authors.forename: Paula
authors.initials: P
authors.lastname: Benny
authors.forename: Clarice
authors.initials: C
authors.lastname: Chen
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Wang
authors.forename: Raj
authors.initials: R
authors.lastname: Rajagopalan
authors.forename: Michael
authors.initials: M
authors.lastname: Raghunath
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight
chemical_list: D046911:Macromolecular Substances; D003094:Collagen; D020778:Matrix Metalloproteinase 2