Transport and Rate Phenomena in Biological Systems

1. Transport and Rate Phenomena in Biological Systems Redux

2. Molecules • They can only do two things: • They react • They move • They are the most important elements in biological systems. • Atoms acquire meaning only in molecules. • All larger-scale entities acquire their ultimate meaning and explanation in molecules.

3. Molecules deliver: • Messages • Material – mass, energy Molecular delivery is particularized by packaging what is to be delivered (message or material) so that only intended recipients are reached. Compare with path-particularized systems.

4. Molecular Motion • Convection • Diffusion • Convective diffusion • Compartments

5. Compartment Representations • Input and output via convection, permeation – passive, permease-driven, active and coupled transport • Accumulation with and without volume change • Reaction: equilibrium, power-law, enzymatic.

6. Reaction • A few reactions among many are rate limiting. Others equilibrate either with reactants or products of rate-limiting processes. • In processes involving both reaction and transport, rate-limiting step may be of either type.

7. Enzyme reactions • Linear in enzyme concentration. • Regulatible ('allosteric effectors') • Substrate dependencies: • First-order at low concentration • Zero-order at high concentration • Enzyme reactions are usually irreversible. • Enzymes are catalysts – they never change an equilibrium– only the rate.

8. Permeases • Can be regarded as enzymes that facilitate transport rather than reactions. • Unlike enzymes, permeases do show reversible behavior. • Models exist for both facilitated (not active) and active transport.

9. Ionic equilibria and membranes • Not considered in these lectures. • May be important – especially in neural cells.

10. Cooperativity • Desirable biological function that supports homeostasis. • Generated by multiple mechanisms. • Expressed in terms of "Hill Functions":

11. Steady State • All variables of interest have the same value at all moments of observation • Steady state is a property of the system and the frame of reference. • Steady state means, at the most fundamental level, no change in accumulation. • Cyclic and "practical" steady states.

12. Cells • A cell • Cohorts of cells • normally asynchronous • synchronization • cyclic and sequential behavior is concealed in cohort-scale measurements.

13. When is a cell not one compartment? • When it is a nerve cell • When its "organelles" must be considered: • Nucleus • Mitochondria • Processing elements • When related chemical species are considered: finite-rate chemical transformations define compartments, too.

14. Macroscopic Problems: Cell Aggregates, Organs • All basic representations are useful if properly reinterpreted: • What goes in, plus what is made, minus what goes out, is always what accumulates. But one must measure what is defined, or define what is measured! • The art (kunst) that must be added to the science (wissenschaft) of macroscopic analysis is picking the right compartments and the right "entities" to follow.

15. Genomics • The concept of the genome and the cells. • Regulation of homeostasis • Control of Development • Reversibility of the normally unidirectional development pathway.

16. The Goodwin Equations • Gene transcription • mRNA translation • Product synthesis. • Feedback to the genome.

17. Gene transcription • one or two genes are transcribed to mRNA by RNAP's controlled by transcription factors. • (Constituitive genes) • Inducing and repressing transcription factors • Attenuation • "Cross-talk" among genes.

18. mRNA translation • mRNA's are generated by transcription, destroyed by a first-order reaction, exist at a steady-state level. Normal and abnormal destruction kinetics – apoptosis. • Ribosomes copy instructions in mRNA into proteins. Some of these are final products. Many are catalysts (enzymes, permeases, signal molecules) that control the formation of a 'final' product.

19. Product Synthesis • Some synthesized products are molecules that feed back information to regulate the geneome: transcription factors. Transcription factors are frequently in "apo" form (incomplete, inactive) and must combine with small molecules to become active. • All products are candidates for destructive processes that may be 'smart' or 'dumb'.

20. Goodwin Equations as a feedback system • Equations thus constitute a genome-cell feedback system. • Positive feedback is not seen as destructive in biological systems because of saturation phenomena and developmental requirement. • Intercellular feedback – to synchronize clones and inter-relate different cell lines.

21. "Tissue Engineering" • "Ultimate*" solutions in the repair of deformed, damaged, or prematurely aged tissue. • Redirect the natural system. • Timing issues • New cells, old cells, transitional states. * If you are going to predict the future, do it often. J.K. Galbraith