Outline. Introduction, program and reference textbooks A few definition and facts Modeling of biological systems:

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1 Introduction 1

2 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 2

3 Outline Introduction, program and reference textbooks 3

4 Program of the Course The program is available at the following links in Italian: PaginaADErogata.do;jsessionid=324CBC945F4B8ED7068BE5FCFC8 B9CCD? ad_er_id=2015*n0*n0*s1*19968*19133&anno_accademico =2016&mostra_percorsi=S or in English: PaginaADErogata.do;jsessionid=324CBC945F4B8ED7068BE5FCFC8 B9CCD? cod_lingua=eng&ad_er_id=2015*n0*n0*s1*19968*19133&ann O_ACCADEMICO=2016&mostra_percorsi=S 4

5 Reference textbooxs Phillips et al., Physical Biology of the Cell, 2 nd 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: pboc2/home.html 5

6 Reference textbooxs Philip Nelson, Biological Physics, Updated 1 st Edition (2008), Editor W. H. Freeman & Company Clear and exhaustive book on physical phenomena dictating behaviors of biological systems. New can be found here: Catalog/product/biologicalphysicsfirstedition-nelson Free (old, uncorrected) pdf found here: kasper.peeters/pdf/nelson_free.pdf 6

7 Outline Introduction, program and reference textbooks A few definition and facts 7

8 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 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

9 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 P % Lipid Carbohydrate 9

10 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 10

11 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 11

12 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 ) 12

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. 13

14 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 14

15 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. 15

16 Modeling to catch key features Models of DNA 16

17 Modeling to catch key features Models of Protein Models of Water 17

18 Modeling to catch key features Models of Membranes 18

19 Modeling to catch key features Models of a bacterium: E. coli 19

20 Modeling to catch key features Modeling Mitochondria From experimental data Cryo-electron microscopy Electron micrograph 20

21 Modeling to catch key features Modeling Mitochondria to cartoon models of structure and functions 21

22 Modeling to catch key features Modeling Mitochondria to cartoon models of structure and functions 22

23 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!!! 23

24 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). 24

25 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 25

26 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). 26

27 Key rules of thumb in biology 27

28 Key rules of thumb in biology More numbers at the BioNumbers website: 28

29 References Books Phillips, chap. 1 Online resources 29

F. Piazza Center for Molecular Biophysics and University of Orléans, France. Selected topic in Physical Biology. Lecture 1

Zhou Pei-Yuan Centre for Applied Mathematics, Tsinghua University November 2013 F. Piazza Center for Molecular Biophysics and University of Orléans, France Selected topic in Physical Biology Lecture 1