Method for finding metabolic properties based on the general growth law. Liver examples. A General framework for biological modeling

We propose a method for finding metabolic parameters of cells, organs and whole organisms, which is based on the earlier discovered general growth law. Based on the obtained results and analysis of available biological models, we propose a general framework for modeling biological phenomena and discuss how it can be used in Virtual Liver Network project. The foundational idea of the study is that growth of cells, organs, systems and whole organisms, besides biomolecular machinery, is influenced by biophysical mechanisms acting at different scale levels. In particular, the general growth law uniquely defines distribution of nutritional resources between maintenance needs and biomass synthesis at each phase of growth and at each scale level. We exemplify the approach considering metabolic properties of growing human and dog livers and liver transplants. A procedure for verification of obtained results has been introduced too. We found that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per day, and verified this using the proposed verification procedure. We also evaluated consumption rate of nutrients in human livers, determining it to be about 0.088 gram of nutrients per cubic centimeter of liver per day for males, and about 0.098 for females. This noticeable difference can be explained by evolutionary development, which required females to have greater liver processing capacity to support pregnancy. We also found how much nutrients go to biomass synthesis and maintenance at each phase of liver and liver transplant growth. Obtained results demonstrate that the proposed approach can be used for finding metabolic characteristics of cells, organs, and whole organisms, which can further serve as important inputs for many applications in biology (protein expression), biotechnology (synthesis of substances), and medicine.Comment: 20 pages, 6 figures, 4 table

Physical paradigm of Life as a generalization of biochemical conception. A Physical law governing life origin and development

The present view of biological phenomena is based on a biomolecular paradigm that development of living organisms is entirely defined by information stored in a molecular form as some genetic code. However, new facts and discoveries indicate that biological phenomena cannot be reduced to a biomolecular realm alone, but are also governed by mechanisms of other nature. These mechanisms, acting in tight cooperation with biochemical mechanisms, define life cycles of individual organisms, and, through this, the origin and evolution of the living world. Here, we present such a physical mechanism (General growth law), which represents a new physical law of nature acting at cellular, organ, system and whole organism levels, directing growth and reproduction together with biomolecular mechanisms. It imposes uniquely defined constraints on distribution of nutrients between biomass production and maintenance, thus defining the composition of biochemical reactions, their change and irreversibility during the organismal life cycle. Mathematically, this law is represented by the growth equation. Using this equation, we introduce growth models and explain division mechanisms for unicellular organisms. High adequacy of obtained results to experiments proves validity of the General growth law and of the new physical paradigm of Life based on this law.Comment: 38 pages, 8 figures, 1 table. Analysis of general principles of Life organization was added, as well as new material and two figures. In particular, analysis of views of E. Schrodinger, whose famous lectures contributed to origin of a biochemical paradigm, exposes what assumptions led him to make inaccurate conclusions. A new, more general physical paradigm of Life was propose

A Method for Modeling Growth of Organs and Transplants Based on the General Growth Law: Application to the Liver in Dogs and Humans

Understanding biological phenomena requires a systemic approach that incorporates different mechanisms acting on different spatial and temporal scales, since in organisms the workings of all components, such as organelles, cells, and organs interrelate. This inherent interdependency between diverse biological mechanisms, both on the same and on different scales, provides the functioning of an organism capable of maintaining homeostasis and physiological stability through numerous feedback loops. Thus, developing models of organisms and their constituents should be done within the overall systemic context of the studied phenomena. We introduce such a method for modeling growth and regeneration of livers at the organ scale, considering it a part of the overall multi-scale biochemical and biophysical processes of an organism. Our method is based on the earlier discovered general growth law, postulating that any biological growth process comprises a uniquely defined distribution of nutritional resources between maintenance needs and biomass production. Based on this law, we introduce a liver growth model that allows to accurately predicting the growth of liver transplants in dogs and liver grafts in humans. Using this model, we find quantitative growth characteristics, such as the time point when the transition period after surgery is over and the liver resumes normal growth, rates at which hepatocytes are involved in proliferation, etc. We then use the model to determine and quantify otherwise unobservable metabolic properties of livers.Comment: 13 pages, 6 figure

Dimensions of geometrical models of dogs’ livers (absolute liver size).

<p>Dimensions of geometrical models of dogs’ livers (absolute liver size).</p

Input parameters for a human liver model for absolute volume calculations.

<p>Input parameters for a human liver model for absolute volume calculations.</p

Cumulative amounts of nutrients going to maintenance needs and biomass production.

<p>Cumulative amount of nutrients consumed by the liver of dog 1 for maintenance and biomass production during liver regeneration, depending on time.</p

Distribution of nutrients in liver.

<p>Nutrients are used for biomass synthesis and maintenance needs in the liver. Processed nutrients go to the rest of an organism.</p

Distribution of nutrient influx.

<p>How much nutrients go to liver maintenance needs and to biomass synthesis depending on time for dog 1. Nutrient influx .</p