Synergistic rate boosting of collagen fibrillogenesis in heterogeneous mixtures of crowding agents.
The competition for access to space that arises between macromolecules is the basis of the macromolecular crowding phenomenon, known to modulate biochemical reactions in subtle ways. Crowding is a highly conserved physiological condition in and around cells in metazoans, and originates from a mixture of heterogeneous biomolecules. Here, using collagen fibrillogenesis as an experimental test platform and ideas from the theory of nonideal solutions, we show that an entropy-based synergy is created by a mixture of two different populations of artificial crowders, providing small crowders with extra volume occupancy when in the vicinity of bigger crowders. We present the physiological mechanism by which synergistic effects maximize volume exclusion with the minimum amount of heterogeneous crowders, demonstrating how the evolutionarily optimized crowded conditions found in vivo can be reproduced effectively in vitro.
†Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117510 Singapore.|‡NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, 117510 Singapore.|§NUS Graduate School for Integrative Sciences and Engineering: Centre for Life Sciences, #05-01, 28 Medical Drive, 117456 Singapore.
Jean-Yves
JY
Dewavrin
†Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117510 Singapore.|‡NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, 117510 Singapore.
Muhammed
M
Abdurrahiem
∥Singapore Bioimaging Consortium, A*STAR, 138667 Singapore.
Anna
A
Blocki
†Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117510 Singapore.
Mrinal
M
Musib
⊥Université d'Orléans and Centre de Biophysique Moléculaire, rue Charles Sadron, F-45071, Orléans, France.
Francesco
F
Piazza
†Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117510 Singapore.|‡NUS Tissue Engineering Programme, Life Sciences Institute, National University of Singapore, 117510 Singapore.|#Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore.
Michael
M
Raghunath
D000818:Animals; D002417:Cattle; D019277:Entropy; D024022:Fibrillar Collagens / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D012867:Skin; D013696:Temperature
D024022:Fibrillar Collagens