• Assignments relating to Brownian ratchets, Dr. Roop Mallik's module and those who missed previous paper-readings: Due date 29-April-2016 @2100h
• Slides relating to the rate-equations, cytoskeleton and modeling approaches uploaded here (password protected)

The introductory course Biophysics (Bio322) on “Physical Biology” of cells sets the stage for a more in depth analysis of some of the issues raised by the often simple concepts touched upon on the previous course. This course, Biophysics II, will deal with molecules, cells and tissues. The novelty of this course will be an introduction to the non-equilibrium processes and how to approach them.

We will begin with a detailed treatment of the one molecule that makes up the largest single population in biological systems- water. Given than most biological systems are in fact out of equilibrium, this course will touch upon some of the most recent theoretical and experimental approaches to understand the out of equilibrium aspects of biophysics. Nerve, muscle and stem-cells will be chosen for special attention as case studies for integration of the hierarchies of molecules and cells that appear to work so flawlessly in our macroscopic world from a biophysics perspective. Research paper reading will highlight case studies of the successful application of physics biological problems.

Continuous assessment will be through:

• Research paper reading
• Assignments
• Labs

1. Mathematics of water: Concepts in fluid dynamics as they apply to cellular scale life
2. Diffusion & Macromolecular crowding
3. Dynamics of macromolecules: Cytoskeleton
4. Molecular motors and Brownian Ratchets: Rate equation paradigm [SLIDES]
5. Biophysics of specialized cell types
   • Muscle cells: Actin-myosin systems
   • Stem cells
6. Tissue dynamics and development
   • Reaction diffusion patterns in development
   • Mechanics and development

Research paper reading assignments

1. Reynolds Number28-29 Jan 2016: Purcell 1977 Life at Low Reynolds Numbers. The famous reprint of a paper that appeared in a book "The Physics of our World"based on a talk given by E.M. Purcell at a Symposium in honour of Victor Weisskopf.
2. Diffusion and measuring it: Conrad W. Mullineaux, Anja Nenninger, Nicola Ray, and Colin Robinson (2006) Diffusion of Green Fluorescent Protein in Three Cell Environments in Escherichia Coli. J. Bact. Vol. 188, No. 10, p. 3442- 3448 [PDF]
3. Crowding: [31 Mar 2016] McGuffee & Elcock (2010) Diffusion, crowding and protein stability in a dynamic molecular model of the bacterial cytoskeleton. PLoS Comp. Biol. Vol. 6, e1000694[PDF]
4. Brownian Ratchets Astumian D. (1997). Thermodynamics and Kinetics of a Brownian Motor. Science 276.[PDF] [Paper reading: 21 Mar 2012]
5. Protein folding Minton, A. P. (2000). Effect of a concentrated 'inert' macromolecular cosolute on the stability of a globular protein with respect to denaturation by heat and by chaotropes: a statistical-thermodynamic model. Biophys. J. 78, 101-109.[PDF]
6. Molecular motors: Bormuth et al. (2009). Protein friction limits diffusive and directed movement of kinesin motors on microtubules. Science 325, 870.[PDF] and supplementary material
7. Tissue mechanics: G Forgacs, R A Foty, Y Shafrir, and M S Steinberg (1998)Viscoelastic properties of living embryonic tissues: a quantitative study. Biophys J. 1998 May; 74(5): 2227-2234.
8. Stem cells: Engler et al 2004 The role of stiffness in stem cell differentiation.

Assignments

• Assignment 1: life in fluids and low Reynolds numbers. DATE for submission: 11-Mar-2016

Additional reading

• Shapere & Wilzek (1989) Geometry of Self-Propulsion at Low Reynolds Numbers
• Bell Model of adhesion and detachment
• Clay mathematics institute and the unsolved mathematical problems on the Navier Stokes Equation: online lectures
• Goeffrey I. Reynold's lectures on Flows at Low Reynolds numbers (vid1), (vid2)- Old but Gold. Lectures recorded for the NSF, USA of a rather old and still very lucid Prof. Talyor, Cambridge University, U.K.
• Chen et al. (1999) Leukocyte rolling motility.
• Minton (2006) How can biochemical reactions within cells differ from those in test-tubes? J.Cell.Sci.119:2863 [PDF]
• Gernot Guigas et al. (2007) The degree of macromolecular crowding in the cytoplasm and nucleoplasm of mammalian cells is conserved. FEBS Letters 581 (2007) 5094 - 5098 [PDF]
• Konopka MC et al. (2006) Crowding and confinement effects on protein diffusion in vivo. J Bacteriol. 2006 Sep;188(17):6115 - 6123.[PDF]

Laboratory protocols

1. Measuring diffusion (Perrin's experiment) [LAB01-PROTOCOL]
   • Date/Time of lab:18, 19 February 2016 @0830h
   • Submission date/time: 03 March 2016 @0900h (in class)
   • Python code for [1D Gaussian fitting]
2. Crowding and enzyme kinetics- A note about the lab, protocol and data [TBA]
   • Date of lab:
   • Submission date:

1. Physical Biology of the Cell- Philips, Kondev, Theriot
2. Biological Physics- Philip Nelson
3. Mechanics of the Cell- David Boal
4. Biological Physics of the Developing Embryo. Gabor Forgacs and Stuart Newman
5. Mechanics of Motor Proteins and the Cytoskeleton- Jonathon Howard
6. Journals:
   • Physical Biology "Physical Biology publishes research on the quantitative characterization and understanding of biological systems at different levels of complexity."
   • Biophysical Journal "Biophysical Journal is the leading international journal for original research in molecular, cellular, and systems biophysics."