Self-Organization and Information Processing: From Basic Enzymatic Activities to Complex Adaptive Cellular Behavior

Abstract

One of the main aims of current biology is to understand the origin of the molecular organization that underlies the complex dynamic architecture of cellular life. Here, we present an overview of the main sources of biomolecular order and complexity spanning from the most elementary levels of molecular activity to the emergence of cellular systemic behaviors. First, we have addressed the dissipative self-organization, the principal source of molecular order in the cell. Intensive studies over the last four decades have demonstrated that self-organization is central to understand enzyme activity under cellular conditions, functional coordination between enzymatic reactions, the emergence of dissipative metabolic networks (DMN), and molecular rhythms. The second fundamental source of order is molecular information processing. Studies on effective connectivity based on transfer entropy (TE) have made possible the quantification in bits of biomolecular information flows in DMN. This information processing enables efficient self-regulatory control of metabolism. As a consequence of both main sources of order, systemic functional structures emerge in the cell; in fact, quantitative analyses with DMN have revealed that the basic units of life display a global enzymatic structure that seems to be an essential characteristic of the systemic functional metabolism. This global metabolic structure has been verified experimentally in both prokaryotic and eukaryotic cells. Here, we also discuss how the study of systemic DMN, using Artificial Intelligence and advanced tools of Statistic Mechanics, has shown the emergence of Hopfield-like dynamics characterized by exhibiting associative memory. We have recently confirmed this thesis by testing associative conditioning behavior in individual amoeba cells. In these Pavlovian-like experiments, several hundreds of cells could learn new systemic migratory behaviors and remember them over long periods relative to their cell cycle, forgetting them later. Such associative process seems to correspond to an epigenetic memory. The cellular capacity of learning new adaptive systemic behaviors represents a fundamental evolutionary mechanism for cell adaptation.

Binding of different substrate molecules at the docking site and the active site of γ-secretase can trigger toxic events in sporadic and familial Alzheimer’s disease

“…For example, disease-causing APPsw mutation can increase enzyme activity by as much as 10 to 50 fold [44]! Such increase in γ-secretase activity is possible only if the enzyme is far below saturation in healthy conditions [17,75]. All enzymes in cells are far below saturation with their substrate [17,45,75,76].…”

“…Such increase in γ-secretase activity is possible only if the enzyme is far below saturation in healthy conditions [17,75]. All enzymes in cells are far below saturation with their substrate [17,45,75,76]. Sub-saturated enzymes give the fastest and linear response to changes in metabolism [17,45,75,76].…”

Associative Conditioning Is a Robust Systemic Behavior in Unicellular Organisms: An Interspecies Comparison

“…This property is originated through complex non-linear interaction of the molecular-metabolic reactions of the cell, which allow self-organization of the biochemical system as a whole. The emergent systemic properties are therefore not found in any of their molecular-metabolic parts, or individual physiological process, and represent an increase in the information and complexity of the cell ( De la Fuente et al, 2021 ).…”

Thermodynamics and Inflammation: Insights into Quantum Biology and Ageing

“…Moreover, the basic physical properties of fatty acid membranes and energy distribution set an upper limit to surface-volume ratios; the energy issue was overcome in eukaryotes by mitochondria, but other thermodynamic limits remain [30,32,33]. When put together with the self-organizing properties of matter and the emergence of dissipative metabolic networks, and the importance of information processing, then it becomes possible to understand how enzyme-based networks gave rise to more complex cellular lifeforms [34]. A key point, however, is that not all structures are dissipative, although they can spontaneously form-but they may well be essential for life, such as membranes.…”

“…Hence, individual species come and go, but life itself remains stable over immense periods of time because, at a global level, it adapts [36]. This is clearly reflected in how self-organization and information in basic enzyme networks form dissipative metabolic networks (DMN) and are also reflected at larger scales, such as cells and whole organisms, and by the ability to learn [34].…”