Physical Biology of the Cell

Introduction
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
1
Outline
•  Introduction, program and reference textbooks
•  A few definition and facts
•  Modeling of biological systems:
–  Models in space and time: from molecules to the cell
–  Quantitative models
–  Mathematizing biology
–  Essential physics & biology to know
–  A few rules of thumb
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
2
Outline
•  Introduction, program and reference textbooks
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
3
Program of the Course
The program is available at the following links
in Italian:
https://webstudenti.unica.it/esse3/Guide/
PaginaADErogata.do;jsessionid=324CBC945F4B8ED7068BE5FCFC8
B9CCD?
ad_er_id=2015*N0*N0*S1*19968*19133&ANNO_ACCADEMICO
=2016&mostra_percorsi=S
or in English:
https://webstudenti.unica.it/esse3/Guide/
PaginaADErogata.do;jsessionid=324CBC945F4B8ED7068BE5FCFC8
B9CCD?
cod_lingua=eng&ad_er_id=2015*N0*N0*S1*19968*19133&ANN
O_ACCADEMICO=2016&mostra_percorsi=S
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
4
Reference textbooxs
Phillips et al., Physical Biology of the Cell, 2nd Edition
(2013), Garland Science Editor
•  Comprehensive and updated book
on physical biology.
•  Access to multimedia and raw data,
hints to solution of problems, etc. at:
http://microsite.garlandscience.com/
pboc2/home.html
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
5
Reference textbooxs
Philip Nelson, Biological Physics, Updated 1st Edition (2008),
Editor W. H. Freeman & Company
•  Clear and exhaustive book on physical
phenomena dictating behaviors of
biological systems.
•  New can be found here:
http://www.macmillanhighered.com/
Catalog/product/biologicalphysicsfirstedition-nelson
•  Free (old, uncorrected) pdf found here:
http://maths.dur.ac.uk/users/
kasper.peeters/pdf/nelson_free.pdf
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
6
Outline
•  Introduction, program and reference textbooks
•  A few definition and facts
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
7
Physical Biology
Why physical biology?

Biology, as any other scientific discipline which aims to be quantitative,
also needs quantitative data and models to greet them and make
reliable predictions.
Physical biology is a relatively new branch of life sciences,
born to satisfy in a notch with the three following needs:
•  The need for quantitative data in biology
•  The need for quantitative interpretative models
•  The need for quantitative predictions by models
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
8
Some general facts of Life
•  In contrast to inert materials, living
entities are made-up by several
macromolecules, which are large,
structurally complex (often built by
repeating blocks) and flexible entities.
Nucleic acid •  Four main macromolecules: nucleic
acids, proteins, carbohydrates, lipids.
Protein •  Few organic atoms form constitutive
blocks (covalently bound) of virtually all
macromolecules of life:
Atom
%
C
O
N
H
S
Lipid Carbohydrate P
10.7 25.7 2.4 60.5 0.13 0.17
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
9
Some general facts of Life
Different macromolecules perform different functions
•  Proteins  structural elements, reaction catalysts, motors, etc…
•  Lipids  barrier between cells and external world,
compartmentalization into organelles, signal transduction, etc…
•  Nucleic acids  memory and operating instructions allowing for
building of new blocks and cell replication.
•  Carbohydrates  energy storage, structural elements (e.g. cell walls),
modify properties of external membranes, etc…
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
10
Outline
•  Introduction, program and reference textbooks
•  A few definition and facts
•  Modeling of biological systems:
–  Models in space and time: from molecules to the cell
–  Quantitative models
–  Mathematizing biology
–  Essential physics & biology to know
–  A few rules of thumb
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
11
Models of life
Requires two main ingredients:
1. A series of experimental facts, grounds on which the model is built:
–  Building blocks of cells are proteins, nucleic acids, fatty acids, etc
–  Membranes of different kinds are responsible for compartmentalization
–  Cells are characterized by temporal cycles
–  …
–  Identify essential features in order to simplify abstraction level
2. A set of physical/chemical principles:
–  Biological processes and systems must obey laws of physics and chemistry
(statistical mechanics, thermodynamics, conservation laws, etc…)
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
12
Models in physics
•  Physics set-up models to describe Nature’s behavior.
•  Models work because hierarchical arrangement of Nature into levels,
corresponding to processes occurring at different length scales.
•  Different strategies to model processes of interest at any given length scale.
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
13
Models in physics
•  Physics set-up models to describe Nature’s behavior.
•  Models work because hierarchical arrangement of Nature into levels,
corresponding to processes occurring at different length scales.
•  Different strategies to model processes of interest at any given length scale.
Goal of biological physics
To understand how life emerges from fundamental
physical and chemical interactions at different
ranges of space and time
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
14
Modeling to catch key features
•  Same object can be modeled in a number of different ways.
–  Depends on set of properties thought to be essential to describe
process/system under study.
•  Models usually complementary to each other.
–  Emphasize different aspects of same object or process.
•  No single representation or model of any system can give
a full understanding of behavior of living cells!
–  Each provides quantitative insights into some aspects of life.
–  All together different models give a more realistic description than each
of them, taken alone, does.
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
15
Modeling to catch key features
Models of DNA Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
16
Modeling to catch key features
Models
of
Protein Models
of
Water Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
17
Modeling to catch key features
Models of Membranes Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
18
Modeling to catch key features
Models of a bacterium: E. coli Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
19
Modeling to catch key features
Modeling Mitochondria From experimental data…
Electron micrograph Cryo-electron microscopy Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
20
Modeling to catch key features
Modeling Mitochondria …to cartoon models of structure and functions
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
21
Modeling to catch key features
Modeling Mitochondria …to cartoon models of structure and functions
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
22
Modeling to catch key features
Modeling Mitochondria …to cartoon models of structure and functions
Don’t forget…
Each of these cartoons (and models) is the results of
decades of efforts aiming to conceptualize a
usually large number of experimental evidences!!!
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
23
Quantitative models
Despite giving key glimpses on process/system being modeled,
usually cartoons fail to reproduce details of experimental data.
They are not quantitative
Indeed…models needs mathematics to pretend being quantitative
(i.e. to reproduce numbers and trends).
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
24
Some key physics laws in biology
…just a few (broad) are sufficient to rigorously interpret many
(not all of course) kinds of quantitative biological data…
•  Harmonic oscillator
•  Ideal gas/solution
•  Two-state systems and Ising statistical model
•  Random walks, entropy, macromolecular structure
•  Poisson-Boltzmann equation
•  Elastic theory of continuum materials
•  Newtonian fluids and Navier-Stokes equation
•  Diffusion and random walks
•  Rate equation models of chemical kinetics
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
25
Some key biological foundations
•  All living organisms are related through descent from a common
ancestor through evolution by natural selection (theory of evolution).
•  DNA is the carrier of genetic information
(genetics and the nature of inheritance).
•  All living organisms are made up of cells (cell theory).
•  A few shared macromolecular assemblies implement similar
functions in different organisms (unity of biochemistry).
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
26
Key rules of thumb in biology
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
27
Key rules of thumb in biology
More numbers at the BioNumbers website: http://bionumbers.hms.harvard.edu
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
28
References
•  Books
•  Phillips, chap. 1
•  Online resources
•  http://www.life.illinois.edu/crofts/bioph354/
Biophysics Course held at Physics Department, University of Cagliari, Italy. Academic Year: 2016/2017. Dr. Attilio Vittorio Vargiu
PLEASE NOTE! This material is meant just as a guide, it does not substitute the books suggested for the Course.
29