Asking biological questions of physical systems: The device approach to emergent properties

Abstract

Life occurs in concentrated 'Ringer Solutions' derived from seawater that Lesser Blum studied for most of his life. As we worked together, Lesser and I realized that the questions asked of those solutions were quite different in biology from those in the physical chemistry he knew. Biology is inherited. Information is passed by handfuls of atoms in the genetic code. A few atoms in the proteins built from the code change macroscopic function. Indeed, a few atoms often control biological function in the same sense that a gas pedal controls the speed of a car. Biological questions then are most productive when they are asked in the context of evolution. What function does a system perform? How is the system built to perform that function? What forces are used to perform that function? How are the modules that perform functions connected to make the machinery of life. Physiologists have shown that much of life is a nested hierarchy of devices, one on top of another, linking atomic ions in concentrated solutions to current flow through proteins, current flow to voltage signals, voltage signals to changes in current flow, all connected to make a regenerative system that allows electrical action potentials to move meters, under the control of a few atoms. The hierarchy of devices allows macroscopic properties to emerge from atomic scale interactions. The structures of biology create these devices. The concentration and electrical fields of biology power these devices, more than anything else. The resulting organisms reproduce. Evolution selects the organisms that reproduce more and thereby selects the devices that allow macroscopic control to emerge from the atomic structures of genes and proteins and their motions.

Multiscale analysis of the effect of surface charge pattern on a nanopore’s rectification and selectivity properties: From all-atom model to Poisson-Nernst-Planck

“…The molecular dimensions of both natural and synthetic nanopores require their modeling on the molecular level provided that we want to understand the molecular mechanisms behind device function and to use that knowledge to design devices with novel properties [21]. Device approach is evidently relevant in biology too [22].…”

Multi-scale modeling shows that dielectric differences make NaV channels faster than KV channels

“…We test this mechanistic hypothesis using a multi-scale modeling approach; that is, an approach that investigates the system at two different time and space scales, in a series of hierarchical computational methods whereby the calculated quantities from a computational simulation at an atomistic scale are used to define the parameters of the model at a coarser, macroscopic scale, that satisfies conservations laws (Eisenberg 2018). In the specific case studied here, of voltage dependent gating, the idea translates into using Brownian modeling to macroscopically describe the system and obtain gating currents, and then using molecular dynamics (MD) simulations to determine the needed free parameters present in the Brownian model.…”

Modeling the Device Behavior of Biological and Synthetic Nanopores with Reduced Models

“…Reduced models are especially useful if we focus on a system as a simple device [ 53 , 54 ]. A device is a black box that responds to some incoming stimuli (input signals) by producing output signals.…”