**8-28-23:** Lecture 1 [Course overview]: wiggling and jiggling, the crowded cell, nonequilibrium processes and the origins of life.

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**8-30-23:** Lecture 2: Molecules diffusing in a volume, transition rates for random motion, probabilities, moments, mean squared displacement (MSD).

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**9-1-23:** Lecture 3: Master equation, deriving equations for the moments of the distribution, calculating the MSD.

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Slides: 1D random walk example

**9-6-23:** Lecture 4: Experimentally measuring MSD, diffusion at different biological scales, the implausibility of giraffes, the continuum approximation and the diffusion equation.

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Slides: Shake, rattle, and roll...
Movie: Diffusion experiment
Slides: Diffusion time scales in biology

*Experimental apparatus design:* Bob Sobin, Rick Bihary; thanks to Pete Kernan for the Rokenbok balls

**9-8-23:** Lecture 5: Continuum approximation continued, solving the diffusion and Fokker-Planck equations, the problem of two molecules diffusing to meet in three dimensions.

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**9-11-23:** Lecture 6: Deriving the mean first passage time, part I: escape times and probabilties, Frogger, discrete recurrence equation.

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**9-13-23:** Lecture 7: Deriving the mean first passage time, part II: continuum equations, Smoluchowski rate limit.

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**9-15-23:** Lecture 8: Tradeoff between reaction speeds and cellular crowding.

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Slides: Crowding and the limits of cell size: parasitic bacteria, giant viruses, and seaweed

**9-18-23:** Lecture 9: Developing a theory of biochemical reaction kinetics.

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Movie:

*Random search of a cancer drug for a protein binding site*,

AVI [credits:

Shan *et al.*, J. Am. Chem. Soc. **133**, 9181 (2011)]

**9-20-23:** Lecture 10: Modeling enzymes via the chemical master equation.

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**9-22-23:** Lecture 11: Approximating chemical dynamics by ignoring fluctuations. Connecting transition rates to energy exchange with the environment.

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**9-25-23:** Lecture 12: Defining temperature via local detailed balance.

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**9-27-23:** Lecture 13: Probability currents, equilibrium and non-equilibrium stationary states, Boltzmann equilibrium.

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**9-29-23:** Lecture 14: Boltzmann equilbrium; coupling system transitions to external work.

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**10-2-23:** Lecture 15: Example of coupling to external work source: light-sensitive proteins.

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Slides: Light-sensitive proteins
Movie:

*Photoactive yellow protein in action*,

AVI [credits:

Schotte *et al.*, Proc. Natl. Acad. Sci. **109**, 19256 (2012)]

Movie:

*Optogenetics*,

MP4 [credits:

Nature Methods **8**, 1 (2011)]

**10-4-23:** Lecture 16: Defining thermodynamic production rates; irreversibility.

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**10-6-23:** Lecture 17: First and second laws of thermodynamics: energy conservation and entropy production.

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**10-9-23:** Lecture 18: Parallels between classical stochastic and quantum systems; the "Heisenberg picture" for the classical master equation.

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**10-11-23:** Lecture 19: Proving the existence of a stationary state; the necessity of dissipated power in nonequilibrium stationary states.

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**10-13-23:** Lecture 20: Origins of life hypothesis #1: the role of UV photons. Recent advances in prebiotic chemistry. The fossil record: stromatolites.

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Slides: Thermodynamics and the origins of life (part 1).

**10-16-23:** Lecture 21: Stromatolites continued. Origins of life hypothesis #2: deep-sea vents. Generalizing the local detailed balance relation: work against pressure, enthalpy, macro- vs. microstates.

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Slides: Thermodynamics and the origins of life (part 2).
Movie:

*Lake Untersee, Antarctica*,

Youtube link
Movie:

*Lost City hydrothermal veents*,

MP4

**10-18-23:** Lecture 22: Coarse-graining biological models, counting microstates, chemical potential.

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**10-20-23:** Lecture 23: Chemical potential in action: biochemical cycles driven by ATP hydrolysis.

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**10-25-23:** Lecture 24: Muscles and membranes.

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Slides: Muscle myosin, ATP hydrolysis at the microscopic level, ATP synthase.
Movie:

*Muscle contraction process*,

Youtube link
Slides: Hydrophobic forces, phospholipid membranes.
Movie:

*Water hydrogen bond network dynamics*,

Youtube link
Movie:

*Water permeation through phospholipid membrane*,

Youtube link

**10-27-23:** Lecture 25: Flexible membranes, permeable and non-permeable molecules.

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**10-30-23:** Lecture 26: Osmotic pressure and its implications for living cells. Charged molecules.

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**11-1-23:** Lecture 27: Cell membranes as capacitors.

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**11-3-23:** Lecture 28: Na and K channels, resting potential, Na/K pumps, total current through membrane.

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**11-6-23:** Lecture 29: Cells as circuits, modeling the axon.

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**11-8-23:** Lecture 30: Setting up the cable equation for neural signals along axons; the need for voltage-gated channels.

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**11-10-23:** Lecture 31: Nerves signals as solitons; the speed of signal propagation.

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**11-13-23:** Lecture 32: ``Wave of death'' in neural signaling; introduction to population genetics: the Wright-Fisher model.

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Slides: Membrane pumps, famous nerves, voltage-gated sodium channels, ``wave of death''

**11-15-23:** Lecture 33: Coalescent theory, neutral mutations, infinite allele model, heterozygosity.

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**11-17-23:** Lecture 34: Effective population size, probability of coalescence going back in time.

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**11-20-23:** Lecture 35: Time-varying populations, mean time to coalescence, dynamics of mutations, substitution rate.

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**11-27-23:** Lecture 36: Dynamics of mutations; the Moran model; deriving Kimura's substitution rate formula.

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**11-29-23:** Lecture 37: Mapping evolution to statistical physics: Sella-Hirsh model; distribution of fitness effects, ratio of non-synonymous to synonymous substitution rates.

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