TY - JOUR
T1 - Phosphates form spectroscopically dark state assemblies in common aqueous solutions
AU - Straub, Joshua S.
AU - Nowotarski, Mesopotamia S.
AU - Lu, Jiaqi
AU - Sheth, Tanvi
AU - Jiao, Sally
AU - Fisher, Matthew P.A.
AU - Shell, M. Scott
AU - Helgeson, Matthew E.
AU - Jerschow, Alexej
AU - Han, Songi
N1 - Funding Information:
ACKNOWLEDGMENTS. The contributions of J.S.S. and the NMR relaxometry, DOSY, and cryo-TEM are funded by the Heising-Simons Foundation. The contributions of J.L. and A.J. and the NMR relaxometry, CEST and CEST simulations are funded by the Heising-Simons Foundatgion and the US National Science Foundation, award no. CHE 2108205. This work was supported in part through the NYU IT High Performance Computing resources, services, and staff expertise. M.S.N. and S.J. acknowledges the support from the National Science Foundation Graduate Research Fellowship under Grant No. 1650114. S.H. acknowledges the support from the US National Science Foundation, award no. CHE 2004217. J.S.S., M.S.N., and S.H. acknowledge the support of Dr. Hongjun Zhou, director of the NMR facility for the UCSB Department of Chemistry and Biochemistry and the support of NSF Major Research Instrumentation award, MRI-1920299, for magnetic resonance instrumentation. The authors acknowledge the support from Dr. Jerry Hu, technical director of spectroscopy facilities for the Materials Research Laboratory and the support of the MRSEC Program of the NSF under Award No. DMR 1720256. Use was made of computational facilities purchased with funds from the National Science Foundation (OAC-1925717) and administered by the Center for Scientific Computing (CSC). The CSC is supported by the California NanoSystems Institute and the Materials Research Science and Engineering Center (MRSEC; NSF DMR 1720256) at UC Santa Barbara.
Publisher Copyright:
© 2022 the Author(s).
PY - 2023/1/3
Y1 - 2023/1/3
N2 - Phosphates and polyphosphates play ubiquitous roles in biology as integral structural components of cell membranes and bone, or as vehicles of energy storage via adenosine triphosphate and phosphocreatine. The solution phase space of phosphate species appears more complex than previously known. We present nuclear magnetic resonance (NMR) and cryogenic transmission electron microscopy (cryo-TEM) experiments that suggest phosphate species including orthophosphates, pyrophosphates, and adenosine phosphates associate into dynamic assemblies in dilute solutions that are spectroscopically "dark." Cryo-TEM provides visual evidence of the formation of spherical assemblies tens of nanometers in size, while NMR indicates that a majority population of phosphates remain as unassociated ions in exchange with spectroscopically invisible assemblies. The formation of these assemblies is reversibly and entropically driven by the partial dehydration of phosphate groups, as verified by diffusion-ordered spectroscopy (DOSY), indicating a thermodynamic state of assembly held together by multivalent interactions between the phosphates. Molecular dynamics simulations further corroborate that orthophosphates readily cluster in aqueous solutions. This study presents the surprising discovery that phosphate-containing molecules, ubiquitously present in the biological milieu, can readily form dynamic assemblies under a wide range of commonly used solution conditions, highlighting a hitherto unreported property of phosphate's native state in biological solutions.
AB - Phosphates and polyphosphates play ubiquitous roles in biology as integral structural components of cell membranes and bone, or as vehicles of energy storage via adenosine triphosphate and phosphocreatine. The solution phase space of phosphate species appears more complex than previously known. We present nuclear magnetic resonance (NMR) and cryogenic transmission electron microscopy (cryo-TEM) experiments that suggest phosphate species including orthophosphates, pyrophosphates, and adenosine phosphates associate into dynamic assemblies in dilute solutions that are spectroscopically "dark." Cryo-TEM provides visual evidence of the formation of spherical assemblies tens of nanometers in size, while NMR indicates that a majority population of phosphates remain as unassociated ions in exchange with spectroscopically invisible assemblies. The formation of these assemblies is reversibly and entropically driven by the partial dehydration of phosphate groups, as verified by diffusion-ordered spectroscopy (DOSY), indicating a thermodynamic state of assembly held together by multivalent interactions between the phosphates. Molecular dynamics simulations further corroborate that orthophosphates readily cluster in aqueous solutions. This study presents the surprising discovery that phosphate-containing molecules, ubiquitously present in the biological milieu, can readily form dynamic assemblies under a wide range of commonly used solution conditions, highlighting a hitherto unreported property of phosphate's native state in biological solutions.
KW - assembly
KW - dark state
KW - dehydration
KW - phosphate
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U2 - 10.1073/pnas.2206765120
DO - 10.1073/pnas.2206765120
M3 - Article
C2 - 36580589
AN - SCOPUS:85145136163
VL - 120
SP - e2206765120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 1
M1 - e2206765120
ER -