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 [email protected] 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