title: Fibrillins, fibulins, and matrix-associated glycoprotein modulate the kinetics and morphology of in vitro self-assembly of a recombinant elastin-like polypeptide.
abstract: Elastin is the polymeric protein responsible for the properties of extensibility and elastic recoil of the extracellular matrix in a variety of tissues. Although proper assembly of the elastic matrix is crucial for its durability, the process by which this assembly takes place is not well-understood. Recent data suggest the complex interaction of tropoelastin, the monomeric form of elastin, with a number of other elastic matrix-associated proteins, including fibrillins, fibulins, and matrix-associated glycoprotein (MAGP), is important to achieve the proper architecture of the elastic matrix. At the same time, it is becoming clear that self-assembly properties intrinsic to tropoelastin itself, reflected in a temperature-induced phase separation known as coacervation, are also important in this assembly process. In this study, using a well-characterized elastin-like polypeptide that mimics the self-assembly properties of full-length tropoelastin, the process of self-assembly is deconstructed into "coacervation" and "maturation" stages that can be distinguished kinetically by different parameters. Members of the fibrillin, fibulin, and MAGP families of proteins are shown to profoundly affect both the kinetics of self-assembly and the morphology of the maturing coacervate, restricting the growth of coacervate droplets and, in some cases, causing clustering of droplets into fibrillar structures.
authors.affiliation: Research Institute, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Judith T
authors.initials: JT
authors.lastname: Cirulis
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bellingham
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: Dirk
authors.initials: D
authors.lastname: Hubmacher
authors.forename: Dieter P
authors.initials: DP
authors.lastname: Reinhardt
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.forename: Fred W
authors.initials: FW
authors.lastname: Keeley
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D004549:Elastin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D000071837:Fibrillins; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008840:Microfilament Proteins / Q000494:pharmacology*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014333:Tropoelastin / Q000737:chemistry / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D000071837:Fibrillins; D006023:Glycoproteins; D008840:Microfilament Proteins; D010455:Peptides; D011994:Recombinant Proteins; D014333:Tropoelastin; C060820:fibulin; D004549:Elastin