PHYS 555 Modern Biophysics – Course Content

Chronological table of course content. Readings, deadlines and links to files.

2025-2026 school year (2025W)

This will be updated (almost) daily as we go through the course. Please check here first if you need anything.

  • Our meeting day/time is Wed, Fri at 10:00am-11:20am.
  • Our meeting place is currently Hennings 309. (3rd floor, corner room with a huge board meeting table)
  • Course credit breakdown is below. We’ll also discuss if this should be tweaked a bit. 
DateDeadlines, tests and reminders In-class topics and materialsTextbook
readings
Week
1

Sept 10 (W) & Sept 12 (F)
HW 1
(due Sept 28)

In-class worksheet for Lect 2

Video Recording Lect 1

Lecture 1 slides

Video Recording Lect2

Lecture 2 slides
Lecture 2 slides, annotated
– Understand the microscopic origins of friction
– Understand the relationship between friction and the diffusion coefficient
– Write a microscopic expression for the diffusion coefficient
– Write and explain Fick’s law
– Relate the thermal velocity of particles in solution to their temperature
– Write and understand the Einstein equation relating the friction coefficient, diffusion constant, and the temperature
– Understand the Reynolds number, and when it is small or large
– Using dimensional analysis to find the relationship between the frictional drag force on a moving sphere
Textbook:
 
13.1 Diffusion in the cell
13.2 Concentration fields and diffusive
flux

Additional Materials:

Nelson-Ch4.1
Rules_of_thumb-numbers

Data Thief Tutorial for HW
Week
2

Sept 17 (W) &
Sept 19 (F)
Video Recording Lect 3

Lecture 3 slides

Lecture 3 slides, annotated

Video Recording Lect 4

Lecture 4 slides

Lecture 4 slides, annotated
Lecture 4 slides Take 2, annotated
– Understand dimensional analysis and how to derive Stoke’s law
– Understand the Gibbs-Boltzmann equation
– Distinguish diffusive from drift flux and write equations for each
– Derive the Einstein relation
– Estimate diffusion coefficients of molecules
– Derive the diffusion equation from continuity and from microtrajectories
– Understand and use binomial probability distributions
Textbook:
13.2 The diffusion equation
13.2.1 Diffusion by summing over microtrajectories
13.2.5 The Einstein relation  

Video Tutorial 1 “6 easy pieces

Einstein’s 1905 paper on diffusion!
Week
3

Sept 24 (W) &
Sept 26 (F)
Lecture 5 slides
Lecture 5 slides, annotated

Video recording Lect 5

Lecture 6 slides
Lecture 6 slides, annotated

Video recording Lect 6
– Probability distributions of random walkers for a large number of steps, in 1D, 2D, 3D.
– Diffusion time
– Biopolymer configurations as random walks
– Return probability and probability of contact formation

Transcriptome (RNA) sequencing

Single-cell RNA sequencing
SMART-seq
Textbook:
8.2.1 Random walk combinatorics
2.1 (pp 44-48) Binomial probabilities
8.2.4 Return probability for random walks – dimension dependence

Picelli & Sandberg Nature Protocols 2014
“Full-length RNA-seq from single cells using Smart-seq2”
Week
4

Oct 1 (W) &
Oct 3 (F)
HW 2 and materials

Lecture 7 slides
Lecture 7 slides, annotated

Video Recording Lect 7

Lecture 8 slides
Lecture 8 slides, annotated

Video Recording Lect 8
– Force-extension relationships for stretched polymers
– Scaling law for the size of a stretched polymer

– Understand the boundary conditions of confined particles vs. confined polymer distributions
– Confined polymers; DNA conformations in the nucleus


Textbook:
14.2.4 (pp 561-562) Self-avoiding polymers;
Flory exponent
8.3.2 Force-extension curves


Week
5

Oct 8 (W) &
Oct 10 (F)
Lecture 9 slides
Lecture 9 slides, annotated

Video Recording Lect 9

Lecture 10 slides
Lecture 10 slides, annotated

Video Recording Lect 10
(sorry no audio and not sure why; I’ll doublecheck the mic set-up next time)
– Fractal dimensions
– Fractal dimension of a random walk

– Einstein derivation of the diffusion equation

– Fluorescence Recovery After – Photobleaching (FRAP); Fourier expansion solutions of the diffusion equation






Textbook:
13.2.3 Diffusion in the cell–FRAP

Youtube tutorial on non-linear curve fitting (in Matlab, Mathematica, R, and Python)
Week
6

Oct 15 (W) &
Oct 17 (F) 
Lecture 11 slides
Lecture 11 slides, annotated

Video Recording Lect 11

Lecture 12 slides
Lecture 12 slides, annotated

Video Recording Lect 12

– Entropy of mixing

– Flory-Huggins theory
– Solvents, polymer melts, expansion & collapse

– Condensates in mixtures; liquid-liquid phase separation
Flory-Huggins theory (reference in Lect 11 slides)

See literature refs in slides
Week
7

Oct 22 (W) &
Oct 24 (F)
HW3 and materials:
Data for prob 1.

Lecture 13 slides
Lecture 13 slides, annotated

Video Recording Lect 13

Lecture 14 slides
Lecture 14 slides, annotated

Video Recording Lect 14
DNA structure — the crumpled globule;

Gene regulation.

– Pol II binding to promoters; probability of binding





Polymer scaling laws
Ideal behavior of polymers in melts
Phase diagrams of polymers in solvents

Textbook:
6.1.2: Statistical mechanics of gene expression: RNA polymerase and promoter 
19.1, 19.2.1 pages 813-814: Gene regulation and activators
Week
8
Oct 29 (W) &
Oct 31 (F)
Lecture 15 slides
Lecture 15 slides, annotated
Video Tutorial on Activators and Repressors of Transcription

Video Recording Lect 15


Lecture 16 slides
Lecture 16 slides, annotated

Video Recording Lect 16
– Tethered activators and gene regulation

– Activators and repressors in gene regulation

– The regulatory factor F_reg

– Fold change (FC)

– Incoherent feed-forward regulation


Textbook:

19.1: Chemical and informational organization in the cell

19.2.1: The molecular implementation of regulation: Promoters, activators, and repressors

19.2 (all subsections): Genetic Networks: Doing the right thing at the right time


Week
9
Nov 5 (W) &
Nov 7 (F)
Lecture 17 slides
Lecture 17 slides, annotated

Video Recording Lect 17


Lecture 18 slides
(This lecture was pptx only)

Video Recording Lect 18
– The Lac operon and DNA looping in regulation.

– DNA looping in repression; Nucleosome remodeling in gene regulation

– Phase separation in transcription; super-enhancers

In-situ hybridization, fluorescence in-situ hybridization (FISH), and immunofluorescence
Textbook:

4.4.1, 4.4.3: The Lac Operon

19.2 DNA looping in repression

6.4.3: Beyond simple ligand receptor binding: The Hill function

Term project instructions
Nov 10-12HW 4 and materials:
Oehler et al. 1994
fig19.27.xlsx
operator_dist_vs_repress.xlsx
READING BREAK
Week
10
Nov 14 (F only)
Lecture 19 slides
Lecture 19 slides, annotated

Video Recording Lect 19
– Elastic Properties of polymers and cellular components

– Young’s modulus, curvature, minimum energy conformations

– Minimum energy conformations
Textbook:
10.1, 10.2 Beams are everywhere: From flagella to the cytoskeleton; Geometry and energetics of beam deformation

10.1, 10.2: Geometry and energetics of beam deformation
Week
11
Nov 19 (W) &
Nov 21 (F)
Lecture 20 slides
Lecture 20 slides, annotated

Video Recording Lect 20


Lecture 21 slides
Lecture 21 slides, annotated

Video Recording Lect 21
– Persistence length of polymers

– The worm-like chain

– Chromatin and nucleosomes

– Nucleosomes in gene regulation
Textbook:
8.2.2: Random Walks; Persistence length
8.2.3: The The Geography of Chromosomes

10.2.2: Persistence Length
10.4.3: Energetics of Nucleosome wrapping

19.2.6: Nucleosomes in gene regulatory architectures
Week
12
Nov 26 (W) &
Nov 28 (F)
Lecture 22 slides
Lecture 22 slides, annotated

Video Recording Lect 22


Lecture 23 slides
Lecture 23 slides, annotated

Video Recording Lect 23

– Nucleosome Remodelling in gene transcription

– Cis-reg architectures in yeast – nucleosome positioning

– MNase-seq; Apparent nucleosome periodicity

– Reconciling nucleosome periodicity and the absence of phase transitions in 1D systems

– Embryonic development in multicellular animals

– Anterior-Posterior patterning; Hox genes and segmentation.
Textbook:
10.4.3: Nucleosome unwrapping thermodynamics

19.2.6: Nucleosomes in gene regulatory architectures

21.3.3: MNase-seq; DNA Sequencing Reveals Patterns of Nucleosome Occupancy on Genomes

20.2.3 Spatial regulation

20.2 Morphogen gradients; The French Flag model
Week 13
Dec 3 (W) &
Dec 5 (F)
Lecture 24 slides
Lecture 24 slides, annotated

Video Recording Lect 24

Lecture 25 slides
Lecture 25 slides, annotated

Video Recording Lect 25

– Spatial patterning, The French flag model, pattern fidelity

– Regulation of genes by enhancers

– Cooperative regulation of Hb by Bcd; precision in spatial expression patterns

– The problem of developmental fidelity

– The Jarzynski equality for non-equilibrium processes
Textbook:
19.2.6: Cooperativity in Bicoid enhancement of the Hunchback gene

20.2.1-3: The French Flag model and thresholding; Statistical mechanics of Bicoid activation

Papers:
Jarzynski PRL 1997
Crooks PRE 1999
Scientist Interviews

Final Term Project
Interview papers:
Takahashi_Sugimoto
Wang_Cottle_Ha
Interviews:
Takahashi
Cottle
Extra topics:
– Role of crowding in cellular environments

– Genomic fluorescence in-Situ Hybridization (FISH) by CRISPR (eSpCas9) + helicase (Rep-X)
(sgGOLDFISH).

– Understand stability points in phase portraits; vector fields
– Linear stability analysis for the genetic switch
– Genetic oscillators
– Ligand receptor binding in cell signaling

– Turing patterns
– Vertebral segment formation
– Notch-delta signaling
– Genome structure
– Phylogenetic trees; evolutionary mechanism
19.3.5: Genetic switches, natural and synthetic

19.4 Cell Signalling

20.3 Reaction-Diffusion and Spatial patterns

20.4 Somitogenesis
20.5 Lateral inhibition
21.2 Gene structure; multiple sequence alignment

Genome Structure