Voltage-gated sodium channels (NavChs) are pore-forming membrane proteins that regulate the transport of sodium ions through the cell membrane. Understanding the structure and function of NavChs is of major biophysical, as well as clinical, importance given their key role in cellular pathophysiology. In this work, we provide a computational framework for modeling system-size-dependent, i.e., cumulative, atomic properties around a NavCh's pore. We illustrate our methodologies on the bacterial NavAb channel captured in a closed-pore state where we demonstrate that the atomic environment around its pore exhibits a bi-phasic spatial organization dictated by the structural separation of the pore domains (PDs) from the voltage-sensing domains (VSDs). Accordingly, a mathematical model describing packing of atoms around NavAb's pore is constructed that allows-under certain conservation conditions-for a power-law approximation of the cumulative hydropathic dipole field effect acting along NavAb's pore. This verified the non-extensitivity hypothesis for the closed-pore NavAb channel and revealed a long-range hydropathic interactions law regulating atom-packing around the NavAb's selectivity filter. Our model predicts a PDs-VSDs coupling energy of similar to 282.1kcal/mol corresponding to a global maximum of the atom-packing energy profile. Crucially, we demonstrate for the first time how critical phenomena can emerge in a single-channel structure as a consequence of the non-extensive character of its atomic porous environment.

Non-extensitivity and criticality of atomic hydropathicity around a voltage-gated sodium channel’s pore: a modeling study / M.N. Xenakis, D. Kapetis, Y. Yang, J. Heijman, S.G. Waxman, G. Lauria, C.G. Faber, H.J. Smeets, P.J. Lindsey, R.L. Westra. - In: JOURNAL OF BIOLOGICAL PHYSICS. - ISSN 0092-0606. - 47:1(2021 Mar), pp. 61-77. [10.1007/s10867-021-09565-w]

Non-extensitivity and criticality of atomic hydropathicity around a voltage-gated sodium channel’s pore: a modeling study

G. Lauria;
2021

Abstract

Voltage-gated sodium channels (NavChs) are pore-forming membrane proteins that regulate the transport of sodium ions through the cell membrane. Understanding the structure and function of NavChs is of major biophysical, as well as clinical, importance given their key role in cellular pathophysiology. In this work, we provide a computational framework for modeling system-size-dependent, i.e., cumulative, atomic properties around a NavCh's pore. We illustrate our methodologies on the bacterial NavAb channel captured in a closed-pore state where we demonstrate that the atomic environment around its pore exhibits a bi-phasic spatial organization dictated by the structural separation of the pore domains (PDs) from the voltage-sensing domains (VSDs). Accordingly, a mathematical model describing packing of atoms around NavAb's pore is constructed that allows-under certain conservation conditions-for a power-law approximation of the cumulative hydropathic dipole field effect acting along NavAb's pore. This verified the non-extensitivity hypothesis for the closed-pore NavAb channel and revealed a long-range hydropathic interactions law regulating atom-packing around the NavAb's selectivity filter. Our model predicts a PDs-VSDs coupling energy of similar to 282.1kcal/mol corresponding to a global maximum of the atom-packing energy profile. Crucially, we demonstrate for the first time how critical phenomena can emerge in a single-channel structure as a consequence of the non-extensive character of its atomic porous environment.
Voltage-gated sodium channels; Scaling; Hydropathicity; NavAb; Non-extensitivity; Criticality
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/825931
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