CBB Unit Seminar

Biology for Physics

Roman Belousov

Erzberger Lab | EMBL, Heidelberg

🙏 Many thanks!

Erzberger group

Sabrina Savino
Valentina Barletta
Samuele Massimi
Michele Lupini
Jenna Elliott
Tim Dullweber
Ian Estabrook
Patrick Jentsch

EMBL

Quail group
Cuylen group
Dey group
DB/Hiiragi (former)
DB/Petridou
DB/Graf

🌍 External: Gulbenkian Institute, Politecnico di Torino, University of Turin, Utrecht University

Publications

Information processing at cellular interfaces (Elliott et al. 2025)
Adaptive droplets (2 x Dullweber et al. 2025)
Coupling of cell shape, matrix and tissue dynamics (Moghe et al. 2025, RB, Savino et al. 2024)
Nuclear deformability in nuclear migration (Maia-Gil et al. 2024)
Embryo‐uterine interaction coordinates mouse embryogenesis during implantation (Bondarenko et al. 2023)

Quantity changes into quality

Microcanonical ensemble out of equilibrium (RB, Elliott et al. 2026)
Action principle for viscoelastic soft matter (Barletta et al. in preparation)

Physics is NOT Mathematics

Mathematics is a language of Physics (but not only)!

What is physics, then?

⟲ Wired up with first principles!

Draco ignivomus

Kingdom: Animalia
Phylum: Chordata
Class: Reptilia-ish
Order: Squamata-adjacent
Family: Draconidae
Genus: Draco
Species: D. ignivomus

Common Fire-Spitting Dragon is a large, volant, hexapedal reptiloform organism distinguished by keratinized cranial horns, extensive patagial wings, reinforced thoracic rib architecture, and a highly expressive glare suggestive of territorial contempt. Adults are typically found in mountainous regions, volcanic slopes, and anywhere livestock are left suspiciously unattended.

What could go wrong?

Describing complex systems

“In physics, interpretability means using concise equations that reliably explain phenomena” [Tan et al. SymTorch (2023)]

🥴? $\psi(x) = \tanh\Bigg(\exp\bigg(\cos\Big(\sin\big(\lambda x\big)\Big)\bigg)\Bigg)$

Desirable, but not sufficient... Interpretability requires a context!

Biology needs physical models

Biologist and physicist — Interpretable as parts of the *whole* coherent theory of life, to fit all our work together!

TF on DNA — Interpretable as parts of the *whole* coherent theory of life, to fit all our work together!

Example: sorting by differential adhesion

Epi & PrE sorting — Epiblast and Primitive Endoderm in the inner cellular mass from a mouse blastocyst.

(CPM) — Poissonian cellular Potts models $P_{dt}(x\pm dx|x) \propto \exp(-\beta \Delta E)$

Scheme of a CPM — Poissonian cellular Potts models $P_{dt}(x\pm dx|x) \propto \exp(-\beta \Delta E)$

Passive sorting

Simulations — Sorting at $T_0 = 37\ ^\circ\mathrm{C}$ and above...

Active sorting

Ensemble theory of equilibrium systems

Microcanonical ensemble:: fix energy $E$ , etc.

Canonical and other ensembles:: fix temperature $T$ , etc.

Ensemble theory of active fluctuations

Lagrange multipliers

Traffic $\Phi$ vs. net current $J$ :

$\Phi = \sum_{\ell > m} (N_{\ell m} + N_{m \ell}) = 2$ cars

$J = \sum_{\ell > m} (N_{\ell m} - N_{m \ell}) = 0$ (opposing directions)

Thermodynamic $\beta = (k_{\rm B} T)^{-1}$: conjugate to the total energy $E$
Traffic affinity $\eta$: conjugate to the traffic $\Phi$ (generalized current); $P_{\ell m} = N_{\ell m}/N_m$ is the fraction of particles jumping from $m$ to $\ell$

Principle of maximum (micro-)caliber

CPM interface — Random walk of an interface between cells in CPMs

Dynamics: $P(x\pm dx|x) \propto \exp(-\beta \Delta E - \eta)$

Active mobility: $\mu(0)\ k_{\rm B} T_0 < \mu(\eta)\ k_{\rm B} T_0$

Maximize path entropy

$N_\ell(t+dt) = \sum_m P_{\ell m}(\beta,\eta) N_m(t)$

Norton ensemble: fix energy $E$ and traffic $\Phi$
Thévenin ensemble: fix temperature $\beta$ and traffic affinity $\eta$

Summary

Biology is complex, but we can still make sense of it with interpretable physical models!
Biology urges physics to (finally) establish the missing first-principles:
- ☑ Ensemble theory of nonequilibrium thermodynamics;
- ☐ Action principle for viscoelastic materials and their thermodynamics;
- ☐ Ensemble theory of phase-separation phenomena and pattern formation.

Thank you for your attention!