Modeling non-genetic information dynamics in cells using reservoir computing (2312.07977v2)
Abstract: Virtually all cells use energy and ion-specific membrane pumps to maintain large transmembrane gradients of Na$+$, K$+$, Cl$-$, Mg${++}$, and Ca${++}$. Although they consume up to 1/3 of a cell's energy budget, the corresponding evolutionary benefit of transmembrane ion gradients remain unclear. Here, we propose that ion gradients enable a dynamic and versatile biological system that acquires, analyzes, and responds to environmental information. We hypothesize environmental signals are transmitted into the cell by ion fluxes along pre-existing gradients through gated ion-specific membrane channels. The consequent changes of cytoplasmic ion concentration can generate a local response and orchestrate global or regional responses through wire-like ion fluxes along pre-existing and self-assembling cytoskeleton to engage the endoplasmic reticulum, mitochondria, and nucleus. Here, we frame our hypothesis through a quasi-physical (Cell-Reservoir) model that treats intra-cellular ion-based information dynamics as a sub-cellular process permitting spatiotemporally resolved cellular response that is also capable of learning complex nonlinear dynamical cellular behavior. We demonstrate the proposed ion dynamics permits rapid dissemination of response to information extrinsic perturbations that is consistent with experimental observations.
- Gatenby RA, Frieden BR. The critical roles of information and nonequilibrium thermodynamics in evolution of living systems. Bull Math Biol. 2013;75(4):589-601.
- Frieden BR, Gatenby RA. Cell development obeys maximum Fisher information. Front Biosci (Elite Ed). 2013;5(3):1017-32.
- Gatenby RA, Frieden BR. Cellular information dynamics through transmembrane flow of ions. Sci Rep. 2017;7(1):15075.
- Yang M, Brackenbury WJ. Membrane potential and cancer progression. Front Physiol. 2013;4:185.
- Adams DS, Levin M. Measuring resting membrane potential using the fluorescent voltage reporters DiBAC4(3) and CC2-DMPE. Cold Spring Harb Protoc. 2012;2012(4):459-64.
- Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952;117(4):500-44.
- Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium. 1985;4(2-3):60-72.
- Ryan MF. The role of magnesium in clinical biochemistry: an overview. Ann Clin Biochem. 1991;28 ( Pt 1):19-26.
- Starr DA. KASH and SUN proteins. Curr Biol. 2011;21(11):R414-5.
- Gurusaran M, Davies OR. A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies. Elife. 2021;10.
- Lin EC, Cantiello HF. A novel method to study the electrodynamic behavior of actin filaments. Evidence for cable-like properties of actin. Biophys J. 1993;65(4):1371-8.
- Odde D. Diffusion inside microtubules. Eur Biophys J. 1998;27(5):514-20.
- Hunley C, Marucho M. Electrical Propagation of Condensed and Diffuse Ions Along Actin Filaments. J Comput Neurosci. 2022;50(1):91-107.
- Tang JX, Janmey PA. The polyelectrolyte nature of F-actin and the mechanism of actin bundle formation. J Biol Chem. 1996;271(15):8556-63.
- Martinac B. The ion channels to cytoskeleton connection as potential mechanism of mechanosensitivity. Biochim Biophys Acta. 2014;1838(2):682-91.
- Shaw JE, Koleske AJ. Functional interactions of ion channels with the actin cytoskeleton: does coupling to dynamic actin regulate NMDA receptors? J Physiol. 2021;599(2):431-41.
- Chifflet S, Hernandez JA. The plasma membrane potential and the organization of the actin cytoskeleton of epithelial cells. Int J Cell Biol. 2012;2012:121424.
- Boldogh IR, Pon LA. Interactions of mitochondria with the actin cytoskeleton. Biochim Biophys Acta. 2006;1763(5-6):450-62.
- Frieden BR, Gatenby RA. Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells. Sci Rep. 2019;9(1):6110.
- Netz RR. Debye-Huckel theory for interfacial geometries. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1999;60(3):3174-82.
- Minoura I, Muto E. Dielectric measurement of individual microtubules using the electroorientation method. Biophys J. 2006;90(10):3739-48.
- Ndzana FI, Mohamadou A. Exact solitary wavelike solutions in a nonlinear microtubule RLC transmission line. Chaos. 2019;29(1):013116.
- Kimball GE CM, Samelson H. A Theory of Polyelectrolytes. J Phys Chem. 1952;56(1):57-60.
- Gatenby RA, Frieden BR. Coulomb interactions between cytoplasmic electric fields and phosphorylated messenger proteins optimize information flow in cells. PLoS One. 2010;5(8):e12084.
- Gatenby R, Frieden BR. Investigating Information Dynamics in Living Systems through the Structure and Function of Enzymes. PLoS One. 2016;11(5):e0154867.