果冻影院

Outline:

The module will provide students with insights into how life works at the level of individual molecules. It will focus on the physical concepts and biological processes discovered in the last decades that underlie molecular machinery of the biological cell. The concepts will be introduced and illustrated by a wide range of phenomena and processes in the cell, including protein and DNA structure, genome organization, polymer mechanics and mechanics of the cytoskeleton, chemical forces and reactions, molecular motors and neural signaling.

Aims:

鈥⑻�听 听Knowledge of the basic cellular components, their structure and function.
鈥⑻�听 听Knowledge and understanding of physical concepts which are relevant for understanding life at the micro- to nanoscale.
鈥⑻�听 听Knowledge and understanding of how these concepts are applied to describe important fundamental processes in the biological cell.

Intended Learning Outcomes:

After completing this module, students should be able to:

鈥� Give a general description of the biological cell and its contents. Describe functions of DNA, proteins and carbohydrates and lipids.
鈥� Explain the concepts of free energy, entropy and Boltzmann distribution and discuss protein structure, ligand-receptor binding and ATP hydrolysis in terms of these concepts.
鈥� Explain the statistical-mechanical two-state model, describe ligand-receptor binding and phosphorylation as two-state systems and give examples of 鈥渃ooperative鈥� binding.
鈥� Describe how polymer structure can be viewed as the result of random walk, using the concept of persistence length, and discuss DNA and single-molecular mechanics in terms of this model.
鈥� Explain the worm-like chain model and describe the energetics of DNA bending and Cytoskeletal deformation; explain how such models are relevant for understanding mechanisms used by cells to grow and divide.
鈥� Explain the low Reynolds-number limit of the Navier-Stoke's equation and discuss its consequences for motion in biological environment.
鈥� Describe simple solutions of the diffusion equation in biological systems and their consequences for understanding diffusion and transport of molecules in cells.
鈥� Explain the concept of rate equations for chemical reactions and apply it to step-wise molecular reactions, enzyme kinetics and polymerization of cytoskeletal filaments.
鈥� Give an overview of the physical concepts involved in the dynamics of molecular motors and apply them to derive quantitative models of motor driven motion and force generation inside the cell.
鈥� Describe neural signaling in terms of propagating action potentials and ion channel kinetics.

Teaching and Learning Methodology:

This module is delivered via weekly lectures supplemented by a series of workshops and additional discussion. Problem-solving skills will be built by setting of problem questions once every three weeks for the students to solve at home.

In addition to timetabled lecture hours, it is expected that students engage in self-study in order to master the material. This can take the form, for example, of practicing example questions and further reading of textbooks and online.

Indicative Topics:

Physical Biology of the Cell
Introduction to the physical biology of the cell; The Central Dogma of Molecular Biology; Structure of DNA, RNA, and Proteins; Overview of functional processes in cells; Quantitative Modelling approaches; Biological Time Keeping.

Statistical Mechanics in the Cell
Deterministic versus Thermal Forces; Equilibrium Models of cellular processes; Free-energy minimization and Entropy; Statistical Microstates and Boltzmann distribution; Partition Function; Applications: Ligand-receptor binding and Ion Channel Gating; Law of Mass Action; Cooperative ligand-receptor binding & Hill Equation.

Two-state Systems
Macromolecules with multiple states; Applications: Ion channel gating, RNA hairpin folding; Gibbs distribution; Chemical Potential; Applications: Ligand-receptor binding, Phosphorylation; Cooperative binding in Hemoglobin and Dimoglobin.

Structure of Macromolecules
Random walk models of polymers; Entropy, Elastic properties and Persistence length of polymers; Chromosome Organization; DNA looping; Single-molecule mechanics; Force- extension relation of random walk polymerMechanics of Biological Filaments [3]
Elasticity theory of Beam deformation; Worm-like chain model; Beam theory applied to the mechanics of DNA and the Cytoskeletal Filaments; Buckling of biopolymers.

Fluid Dynamics in Biology
Navier-Stokes Equation; Viscosity and Reynolds number in cells; Fluid Dynamics of Blood; Mechanics of Leukocyte rolling; Low Reynolds number world; Stokes Flow; Swimming of microorganisms; The Scallop Theorem.

Diffusion in Cells
Active vs Passive Transport in Cells; Fick鈥檚 Law for diffusive transport; Diffusion equation and its solutions; Application: Fluorescence Recovery after Photobleaching; Driven diffusion 鈥� Smoluchowski equation and the Einstein Relation; Diffusion limited capture.

Chemical Reactions in the Cell
Actin-based cell motility; Rate equations for chemical reactions; Decay processes; Biomolecular reactions; Michaelis-Menten and Enzyme kinetics; Polymerization dynamics of cytoskeletal filaments; Dynamic Instability in Microtubules.

Molecular Motors
Molecular motors in the cell; Mechanics of muscle contraction; Stepping dynamics of motors; Rectified Brownian motion versus active force generation; Driven diffusion equation for a molecular motor; multiple-state model for molecular motors; Force generation by polymerization.

Action Potentials in Nerve Cells
Charge state of the cell; Electrochemical equilibrium and Nernst Potential; Two-state model for ion channels; Hodgkin-Huxley model for propagation of action potentials.