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