A eukaryotic cell is not a bag of chemistry. It is a spatial organisation of chemistry — a set of compartments that maintain, against the universal pressure of the second law, distinguishable internal states. Our new Organelles Biophysics course treats the cell as a federation of thermodynamically distinct compartments and asks, throughout, a single question: what physics makes a compartment worth the cost of building it?
Eight Modules
- M0 — Why Compartmentalize? The entropy cost of partitioning, three benefits (concentration, chemical exclusion, regulatory leverage), the thermodynamic taxonomy of organelles.
- M1 — Membrane Biophysics: Canham-Helfrich elastic energy, fluctuation spectrum kBT/(κq4 + σq2), three curvature regimes, spontaneous curvature. Embeds Tom Rapoport’s lecture on how organelles are shaped.
- M2 — The Nucleus as Transport Organelle: NPC architecture, FG-nucleoporin selective phase, Ran-GTP cycle, chromatin as a fractal-globule polymer.
- M3 — Endoplasmic Reticulum: cotranslational translocation through Sec61, folding funnel, calnexin cycle, the UPR ODE system, ERAD. Embeds Rapoport’s lecture on organelle biosynthesis and protein sorting.
- M4 — Mitochondria & Chemiosmotic Coupling: pmf derivation, cristae as saddle-geometry optimisations, Marcus–Hush electron transfer in the ETC, F0F1 rotary motor.
- M5 — Lysosomes & Peroxisomes: V-ATPase set-point equation, pKa engineering of cathepsins, lysosomal storage disorders, peroxisomal biogenesis.
- M6 — Membraneless Organelles & LLPS: Flory–Huggins demixing, multivalent IDPs, nucleoli and stress granules, the FUS/TDP-43 liquid-to-solid aging problem in ALS.
- M7 — The Integrated Cell: MAMs, ER–PM junctions, ER–lysosome contacts, mitochondria–lysosome contacts. Embeds a field-defining lecture on membrane contact sites.
Problem Set with Full Solutions
Eight problems span basic Helfrich calculations, NPC transit-time analysis, F1F0 gear-ratio derivation, Marcus rate optimisation, UPR bifurcation dynamics, Flory–Huggins spinodal derivation, mitochondrial capacitance, and a conceptual integration across modules. Full worked solutions with numerical values are provided in a companion page.
Prerequisites
Graduate / advanced undergraduate level. Statistical mechanics and partial differential equations are assumed; undergraduate biochemistry is sufficient for the biological content. Every biological term is defined on first use.