Lecture 1

Introduction

Goals of the Course and today’s Biological Research

The length and time scales of biological processes

Cell as an elementary unit of life

The unifying molecular paradigm

Prokaryotes and Eukaryotes

The tree of life

Cells are open system operating far from equilibrium

Physics laws hold everywhere

BSCI 338O/BIOL 708O Cell Biology from a Biophysical Perspective

Instructor: Sergei Sukharev sukharev@umd.edu 301-405-6923

Lectures: Tue, Thu 3:30-4:45 pm, PLS 1180

Web http://chemlife.umd.edu/classroom/bsci338-biol708/syllabus.html

Main Text:

Molecular Cell Biology by Lodish et al. (6th or 5th Edition) Freeman & Co., 2007 or 2004

Other helpful reading:

Physical Biology of the Cell by Rob Phillips, Jane Kondev and Julie Theriot. Garland Science 2008

Biological Physics. Energy, Information, Life by Philip NelsonFreeman & Co., 2004

Molecular and Cellular Biophysics by Meyer JacksonCambridge University Press, 2006

Mechanics of Motor proteins and Cytoskeleton by Jonathan HowardSinauer, 2001

Cell Physiology Sourcebook. A Molecular Approach (3d Edition)Edited by Nicholas Sperelakis. Academic Press, 2001

The purpose of the course:

A concise review of major concepts describing cellular function with the focus on unifying principles and mechanisms, with links to the physico-chemical properties of the components; a consideration of the energetic and kinetic aspects of the processes; and the strategies and key techniques used in performing the studies. The course will help students identify interesting mechanistic biological problems that they can pursue in new ways utilizing their unique background.

(not the best way to fix the GPA for struggling pre-meds)

Open-book exams:

Two mid-term exam (30+30% of the total points)

The final scheduled for Wed, May 20, 10:30-12:30, (40% of the grade)

What is today’s Biology?

Primary observation

Accumulation and sorting of phenomenology

Identification of molecular players and compartments

Putting events in causative sequences

Finding and comparing homologous processes/components in other organisms

Separating the essential (minimal) and auxiliary components

Solving structures

Interpreting structures, predicting transition pathways and mechanisms

In the end, THE BEST BIOLOGICAL RESEARCH is a pursuit of THE PHYSICO-CHEMICAL NATURE of a BIOLOGICAL PHENOMENON

Human body ~2 m

Organ, tissue ~10-1 m

Cell ~10-4 - 10-5 m

Subcellular organelle ~ 10-5 - 10-7 m

Macromolecule 10-8 – 10-9 m

Small molecule (solvent) 2.8·10-10 m

Length scale

Macromolecular Scales

From P. Nelson

Population, species lifespan 102-108 yr

Organismal lifespan 1-103 yr

Cell cycle/genome duplication 20 min – 48 hr

Transport reaction rates 102 - 108 s-1

Protein domain movements 10-8 – 10-1 s

Retinal photoisomerization 2·10-13 s

Transcription rate 10 - 20 nucleotides/s

Free sidechain correlation times 10-11-10-6 s

Solvent correlation times 10-10-10-11 s

Time scales

Covalent bond vibration 6·1012 - 1014 s-1

The Tree of Life (Medical School version)

Eubacteria

Archaea

Ciliate: Pramecium

Dictyostelium discoideum

Colonies of alga

Blood cells

Neuron

Intestinal epithelium

Wood

The CENTRAL DOGMA

DNA: Legislative Branch

Proteins: Executive Branch

Genome (Genomics: data mining, sequence assignment)

Proteome (Mass-spectrometry, Proteomics)

Functional traits (Phenotype, function, physiology, biochemistry, biophysics)

Transcription regulation, alternative splicing,

Folding, sorting, post-transcriptional modification, targeting, complex assembly, co-factors, activation,

Transcripts (RT PCR, micro-array analysis)

Translation

1927 1990’s

C6H12O6 + 6O2 686 kcal/mol

30 ADP + 30 Pi 30 ATP +30 H+ + 30 H20

6 CO2 +6H2O

32% efficiencyATP = ADP+Pi

7.3 kcal/mole

219 kcal/mol

Cells are open systems operating far from equilibrium

However many of the “local and fast” events can be treated as equilibrium processes

Keq

Complete equilibrium = death

Principles of Physics hold everywhere(and set their limitations)

++

+

electrometer

voltage-gated channel

kTnekTG

c

o eeP

P //

o

c

Charged transmembrane helix = voltage sensor

Voltage dependence of open probability

unmyelinated fiber myelinated fiber

=regular wire =High-frequency cable