title: Proteoglycans and their heterogeneous glycosaminoglycans at the atomic scale.
abstract: Proteoglycan spatiotemporal organization underpins extracellular matrix biology, but atomic scale glimpses of this microarchitecture are obscured by glycosaminoglycan size and complexity. To overcome this, multimicrosecond aqueous simulations of chondroitin and dermatan sulfates were abstracted into a prior coarse-grained model, which was extended to heterogeneous glycosaminoglycans and small leucine-rich proteoglycans. Exploration of relationships between sequence and shape led to hypotheses that proteoglycan size is dependent on glycosaminoglycan unit composition but independent of sequence permutation. Uronic acid conformational equilibria were modulated by adjacent hexosamine sulfonation and iduronic acid increased glycosaminoglycan chain volume and rigidity, while glucuronic acid imparted chain plasticity. Consequently, block copolymeric glycosaminoglycans contained microarchitectures capable of multivalent binding to growth factors and collagen, with potential for interactional synergy at greater chain number. The described atomic scale views of proteoglycans and heterogeneous glycosaminoglycans provide structural routes to understanding their fundamental signaling and mechanical biological roles and development of new biomaterials.
authors: Faculty of Life Sciences, The University of Manchester, Manchester Institute of Biotechnology , 131 Princess Street, Manchester, M1 7DN, United Kingdom.
authors: Benedict M
authors: BM
authors: Sattelle
authors: Javad
authors: J
authors: Shakeri
authors: Matthew J
authors: MJ
authors: Cliff
authors: Andrew
authors: A
authors: Almond
mesh_terms: D000510:Alpha-Globulins / Q000737:chemistry*; D000818:Animals; D002236:Carbohydrate Conformation; D002356:Cartilage / Q000737:chemistry; D002417:Cattle; D002809:Chondroitin Sulfates / Q000737:chemistry*; D058575:Decorin / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000737:chemistry*; D006801:Humans; D007422:Intestines / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012754:Sharks; D034421:Sus scrofa; D014132:Trachea / Q000737:chemistry
chemical_list: D000510:Alpha-Globulins; D058575:Decorin; C016001:alpha-1-microglobulin; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates
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