Subcellular Systems - Molecular Theory of the Living Cell - page 317

Thermodynamic Requirement : Most, if not all, molecular motions of the intracellular
particles must be driven away from random directions and random durations, utilizing
the free energy supplied by exergonic chemical reactions (e.g., ATP hydrolysis), since
random motions are incompatible with life. (11.14)
Control Information Requirement : The non-random molecular motions of the intracellular
particles must be constrained in space and time by the boundary conditions that embody
both the genetic information (or “internal constraints”) and environmental information (or
“external constraints”). (11.15)
Requirement 11.14 is met by the conformon theory of molecular machines (Ji
1974a, b, 2000, 2004a), according to which all molecular machines (e.g., molecular
motors, ion pumps, and enzymes) inside the cell are driven by sequence-specific
conformational strains called conformons that are generated from exergonic chem-
ical reactions or ligand-binding processes based on the generalized Franck-Condon
mechanisms (Chaps. 7 , 8 ) .
The control information essential for cell functions may be transferred in two
distinct ways - through (a) covalent interactions (e.g., via forming equilibrium
structures such as phosphorylated proteins, RNAs, etc.), and (b) noncovalent
interactions (e.g., via forming dissipative structures such as transient protein
complexes, cytosolic ion gradients, etc.). The former may act as internal constraints
that transmit control information through time, i.e., from one moment to the next
during the lifetime of a cell or from one cell generation to the next, while the latter
may act as external constraints on molecular machines (e.g., membrane potentials,
cytosolic ion gradients, ATP levels in the cytosol, etc.) transmitting control infor-
mation through space, e.g., between the nucleus and the cytosol and between the
cytosol and the extracellular space (Ji 1988). Through these two mechanisms, the
cell can control its molecular processes or events in space and time.
More specifically, the cell must control its molecular processes (conformational
motions, ATP hydrolysis, etc.) that can occur on the subpicosecond (10 12 s)
timescales and the subnanometer (10 9 m) length scales (referred to as the micro-
scopic level) to drive the molecular processes that occur on the time- and length
scales of 10 3 s and 10 5 m, respectively (referred to as the mesoscopic level).
Thus, the micro- and mesoscopic levels are separated from each other by approxi-
mately 10 orders of magnitude in time- and mass scales. The coupling of events
separated by such divergent temporal and spatial scales will be referred to as the
micro-meso coupling . The fundamental significance of the micro-meso coupling in
biology stems from the fact that the free energy needed to drive all living processes
inside the cell ultimately derives from exergonic chemical reactions (e.g., oxidation
of glucose, ATP hydrolysis) that occur only on the microscopic level. The question
as to how the cell accomplishes the micro-meso couplings across the spatiotempo-
ral gaps separated by 10 orders of magnitude is one of the most challenging
problems facing the contemporary biology, since they underlie most of the
unsolved problems in molecular and cell biology, including the mechanisms of
force generation in muscle, gene expression in the nucleus, and morphogenesis of
living tissues (Sect. 15.1 ).