Abstract

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 and constraints for many applications in biology (such as protein expression), biotechnology (synthesis of substances), and medicine.

Highlights

  • The general growth law is one of the major mechanisms of Nature governing evolutionary development of living species and their individual growth and development at different spatial levels, from cellular components to whole organisms [1]

  • We present a continuation of this study, introducing a general method for finding metabolic parameters, such as nutrient influx consumed by growing and grown cells and organs in order to support different functions. (Nutrient influx is the rate at which nutrients are consumed by organisms or its constituents.) Once we know nutrient influx, we can find integral metabolic characteristics, such as accumulated amount of nutrients required to support biomass synthesis and maintenance needs for each phase of growth or for a certain period

  • We demonstrate method’s efficiency by applying it to study of liver metabolism, using experimental data on growth of liver transplants in dogs [2], when whole small livers were transplanted from small dogs to big dogs, and liver grafts in recipients and liver remnants in donors in case of humans [3,4]

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Summary

Introduction

The general growth law is one of the major mechanisms of Nature governing evolutionary development of living species and their individual growth and development at different spatial levels, from cellular components to whole organisms [1]. Results of recent studies and particular applications of the general growth law presented in [1,12,15,16,17,18,19], with major work [1], allow finding metabolic parameters, which effectively define integral constraints required for complete models of biochemical mechanisms. We rely on the same experimental data from works [2] for dog livers and [3,4] for human livers This application of the general growth law is unique in that regard that it allows interrelating general characteristics of organisms (mass, volume and geometrical parameters), directly to metabolic properties such as nutrient consumption rate and distribution of nutritional resources between the maintenance needs and biomass synthesis. Simplicity and elegancy of application of the general growth law to this important task makes the approach very effective

Finding Metabolic Characteristics from the Growth
Finding Metabolic Characteristics for Livers
Requirements and Criteria for Developing Biological Models
Findings
Conclusion
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