Opportunity for candidates with BSc: Explore how the interplay of biological building blocks can generate life and how to replicate life-like systems. Combine new technologies by learning-by-doing and creatively use biological substances to gain new insights and invent applications in the life sciences. The direct-track PhD program Matter to Life is part of the Max Planck School Matter to Life.
Please refer to campus.tum.de for lectures & seminars that are taught currently by members of this laboratory. Below please find the lecture material for the course on mechanics and dynamics of biomacromolecules taught by HD within the biophysics master's program of TUM.
This course should contain most of what you should know about the physical and chemical aspects of biological macromolecules (and their interactions) to carry out research in molecular and cellular biophysics. The author of the lecture files is H.Dietz, but some of the slides contain privileged material from other sources. The files are for your personal use only.
SUMMER 2019: Please see here for course materials https://shwca.se/DIETZLABTEACHING.
Chapter 1 - Introduction
Administrative stuff
On biological machines
E.coli book-keeping
Molecular length- and time scales, forces, energies
Chapter 2 - Life in bitumen
Fluid dynamics:
- Navier-Stokes Equation
- Flow through narrow channels
- The Reynolds Number
- The Low-Reynolds regime: Life in bitumen.
Chapter 3 - Life in a thermal hurricane
Basics of diffusion:
- The microscopic perspective
- Smoluchowski Equation / Diffusion Equation
- Transport with Fokker-Planck
- Einstein Relation
- Crowded Environments
- Diffusion as Transport Mechanism
Chapter 4 - Interlude: Gene regulation
The regulation of lactose metabolism in E.coli. (descriptive)
- Regulated recruitment
- RNA polymerase, Lac repressor, CAP activator
- Protein-DNA recognition
- Detection of physiological signals
Chapter 5 - Macromolecule meets macromolecule
Fundamental reaction speed limits:
- Free diffusion to capture
- Free diffusive release
- Diffusion to capture / release in potentials
- Reduction of dimensionality
- Kramers and Arrhenius
Chapter 6 - Lost in transition
Rate equations and equilibrium aspects of:
- Irreversible Decay
- Reversible two-state system
- Two-state systems under force: shifted equilibrium, accelerated rates
Interlude 2:
- Protein unfolding under force
- Case study: 3D Mechanics of Green Fluorescent Protein
Chapter 7 - Let's stick together
Dynamics of bimolecular reactions:
- Steady-state characteristics, Gibbs Free Energy
- Equilibration time scales
- Concentration / Affinity jumps
- Cooperative binding: Molecular logic
- Response function of a repressed gene
- Response function of a gene controlled by an activator
Chapter 8 - Enzyme kinetics
Dynamics of enzymatic catalysis:
- How enzymes can speed up chemical reactions
- Michaelis-Menten enzyme kinetics
- Non-Michealis-Menten kinetics
- Enzyme activation
- Energy available for work by substrate flux
- Examples: ATP Synthase, Kinesin
Chapter 9 - Polymer elasticity and molecular random walks
Shape and mechanics of polymeric chains:
- The 1D random chain: end-to-end distance, entropic elasticity
- The freely-jointed chain model
- Bending mechanics of slender rods
- Persistence length as a measure for stiffness
- The worm-like chain
Chapter 10 - Beams and polymers are everywhere!
A few examples on where bending and stretching matters:
- Beams in gene regulation: the case of the lac repressor and other suspects
- Beams in the cytoskeleton: Actin structure and mechanics, other filaments
- Fiber stretching and molecular unfolding in blood clotting
- Polymer elasticity as a molecular ruler for structure determination.
- A few afterwords
Part II - Motors, membranes, and biological design principles
Administrative stuff, syllabus, and course calendar
- contains instructions for how to prepare the seminar project
Chapter X -Stochastic Chemical Kinetics
- Reminder probability theory
- Specifying a chemical system
- The specific probability rate constant
- Collisions with impact threshold
- The chemical master equation (CME)
- Solving the CME
- The Gillespie algorithm
Chapter 11 - Translational molecular motors: an overview
A crash-course in molecular motor traffic:
- Types of motors
- Methods of experimental analysis
- Kinesin: structure, stepping behaviour etc
- Dynein: structure, stepping behaviour etc
- Myosin: structure, stepping behaviour etc
Chapter 12 - Molecular motors as random walkers
Understanding molecular motor behaviour:
- The one-state-model
- The one-state-motor under force
- Ratchet-shaped energy profiles
- Fluctuation analysis
- The two-state-model
Chapter 13 - ATP Hydrolysis as a source of energy
The molecular details of ATP hydrolysis
- ΔG when ATP is split into ADP and P
- Motors move along a ΔG gradient
- Motors move faster with higher [ATP]
- Structure of ATP and the hydrolysis reaction
- At least 8 distinct states are involved in motor stepping
- Case study: the complete ATP hydrolysis cycle of Myosin II
Chapter 14 - ATP Synthesis by ATP Synthase
ATP Synthase: a marvelous mechano-chemical factory
- Structure of ATP Synthase
- F1-Motor catalyzes ATP hydrolysis and synthesis
- Experimental evidence
- F1 ATPase hydrolysis cycle
- F0-Motor rotation mechanism
- Minimum delta pH for ATP synthesis
Chapter 15 - How cytoskeletal filaments might form
Polymerization kinetics
- The equilibrium polymer
- Nucleated growth
- Treadmilling
- Dynamic instability
- Multi-stranded filaments
- Propulsion by polymerization
Chapter 16 - Kinetic Proofreading & Robustness
The concept of proofreading in
- protein translation
- immuno recognition
The concept of robustness in
- bacterial chemotaxis
And some notes on translocation ratchets.
Chapter 17 - Reaction and Diffusion.
More on reactions.
- beyond bimolecular reactions
- feedback, oscillations
Reminder on diffusion.
Reaction - Diffusion Equations
- typical structure
- spatial and temporal discretization