Proteoglycans and Their Heterogeneous Glycosaminoglycans at the Atomic Scale Benedict M. Sattelle Javad Shakeri Matthew J. Cliff Andrew Almond 10.1021/bm5018386.s004 https://acs.figshare.com/articles/dataset/Proteoglycans_and_Their_Heterogeneous_Glycosaminoglycans_at_the_Atomic_Scale/2048880 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. 2015-12-17 07:35:11 proteoglycan size hexosamine sulfonation Atomic ScaleProteoglycan spatiotemporal organization growth factors Uronic acid iduronic acid block copolymeric glycosaminoglycans glucuronic acid Heterogeneous Glycosaminoglycans scale views chain plasticity sequence permutation chain number interactional synergy dermatan sulfates glycosaminoglycan chain volume glycosaminoglycan unit composition glycosaminoglycan size scale glimpses extracellular matrix biology