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Transport and Rate Phenomena in Biological Systems. Redux. 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.

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molecules
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.
molecules deliver
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.

molecular motion
Molecular Motion
  • Convection
  • Diffusion
  • Convective diffusion
  • Compartments
compartment representations
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.
reaction
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.
enzyme reactions
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.
permeases
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.
ionic equilibria and membranes
Ionic equilibria and membranes
  • Not considered in these lectures.
  • May be important – especially in neural cells.
cooperativity
Cooperativity
  • Desirable biological function that supports homeostasis.
  • Generated by multiple mechanisms.
  • Expressed in terms of "Hill Functions":
steady state
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.
cells
Cells
  • A cell
  • Cohorts of cells
    • normally asynchronous
    • synchronization
    • cyclic and sequential behavior is concealed in cohort-scale measurements.
when is a cell not one compartment
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.
macroscopic problems cell aggregates organs
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.
genomics
Genomics
  • The concept of the genome and the cells.
  • Regulation of homeostasis
  • Control of Development
    • Reversibility of the normally unidirectional development pathway.
the goodwin equations
The Goodwin Equations
  • Gene transcription
  • mRNA translation
  • Product synthesis.
  • Feedback to the genome.
gene transcription
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.
mrna translation
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.
product synthesis
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'.
goodwin equations as a feedback system
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.
tissue engineering
"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