Physics of the living cell
Prerequisites
IV and V year students
(Exam can also be borrowed by postgraduate students, recommended for "Nanosciences", "MEMOS", "Data Science", "Physics", "Neurosciences")
Programme
Physics of the living cell
(basic principles, open questions, advanced methods)
The Cell as a complex, dynamic, physical system: basic concepts and open questions
- The cell structure: general principles
o DNA: an “aperiodic crystal”
o Prokaryotes vs Eukaryotes
o Compartmentalization
o The central dogma: does it still stand?
- The cell boundaries
o Membrane structure: general principles
o From homogeneity to heterogeneity
o Do lipid rafts exist?
- The sub-cellular scale:
o “The postal service of the cell”: the endocytic/secretory pathway (case studies on: clathrin-coated pits and insulin secretory granules)
o The nuclear pore complex: an organelle, a machine, or just an hole?
o Phase separation in the cell and membrane-less organelles
- The role of molecular diffusion/transport:
o Life in 2D: diffusion/transport on the membrane.
o Life in 3D: diffusion/transport in the intracellular environment
o Diffusion/transport between nucleus and cytoplasm
o Molecular motors
How do we know? (Fluorescence) microscopy to scoop the biological world
- (Auto)Fluorescence-based methods
o Intrinsic cellular fluorophores
o “Label-free” microscopy: applications
- Genetically-encoded fluorescence
o The Green Fluorescent Protein and its mutants: from labeling to sensing
o New frontiers: organic dyes for live-cell imaging
- Fluorescence-based methods to probe molecular interactions:
o Forster Resonance Energy Transfer
o Single molecule/super-resolution methods to unveil protein clusters
- Fluorescence-based methods to probe molecular dynamics):
o Perturbation-based methods: e.g. Fluorescence Recovery After Photobleaching
o Fluctuation-based methods: from single-point to spatiotemporal Fluorescence Correlation Spectroscopy
o Localization-based methods: Single-Particle Tracking
o Feedback-based orbital tracking and imaging
The Cell as an excitable system: the role of Ion exchanges
o A cell as a communication channel: how do we codify information in a living system? How do we create a communication channel? The limits of diffusion as a communication channel
o How do we codify the internal state of an excitable cell? Membrane potential as an equilibrium between diffusion and electrophoretic drift: Nernst Equation
o Information coding and transmission by propagation of the membrane potential: equivalent circuits and telegraph equation
o Life is complicated: non-linear telegraph equation. Hodgkin and Huxley model for the action potential
o Further element of complexity: the Nernst-Plank equation.
o Intercellular communication: synaptic transmission. From the equivalent electrical model to signal transmission and elaboration.
o The consequences of networking cells: oscillations and rhythm in the brain
How do we know? Methods for studying signal processing in the living brain
o Measuring ionic currents: from the squid axon to patch clamp.
o The brain as a network: optical methods for decoding the brain internal state
o Decoding activity from far away: population activity mirrored by the extracellular electric field. Spectral analysis for beginners.
Educational aims
Educational goals: Learning the basic principles that regulate the structure and activity of cells, with particular attention to nanoscale processes. Learning of the most advanced methods for studying the mechanisms presented. Knowledge of the frontier areas of research on the cellular and sub-cellular scale.
Bibliographical references
Phillips et al. Physical Biology of the Cell