BME 285: Biology for Biomedical Engineers
Estimated study time: 8 minutes
Table of contents
Sources and References
Primary texts — Alberts et al., Molecular Biology of the Cell, 7th ed. (Garland). Nelson and Cox, Lehninger Principles of Biochemistry, 8th ed. (W. H. Freeman).
Supplementary texts — Lodish et al., Molecular Cell Biology, 9th ed. (W. H. Freeman). Saltzman, Biomedical Engineering: Bridging Medicine and Technology, 2nd ed. (Cambridge). Palsson, Tissue Engineering, 2nd ed. (Cambridge).
Online resources — MIT OCW 7.01SC Fundamentals of Biology and 20.310J Molecular, Cellular, and Tissue Biomechanics. NCBI Molecular Biology of the Cell open access. Protein Data Bank. Cold Spring Harbor Laboratory DNA Learning Center open tutorials. Khan Academy Biology (open reference).
Chapter 1: The Chemistry of Life
1.1 Water, pH, and Buffers
Water is the solvent of life. Its polarity, hydrogen bonding, and high dielectric constant support macromolecule folding and ion transport. Physiological pH ≈ 7.4 is maintained by the carbonic-acid/bicarbonate buffer:
\[ \mathrm{CO_2} + \mathrm{H_2O} \rightleftharpoons \mathrm{H_2CO_3} \rightleftharpoons \mathrm{H^+} + \mathrm{HCO_3^-} . \]The Henderson–Hasselbalch equation
\[ \mathrm{pH} = \mathrm{p}K_a + \log\frac{[\mathrm{A^-}]}{[\mathrm{HA}]} \]quantifies buffer capacity and underlies device design for blood-contacting materials and drug formulations.
1.2 Building Blocks
Four classes of biomolecules dominate: amino acids, carbohydrates, lipids, and nucleotides. Each is a modular unit whose polymer — proteins, polysaccharides, lipid bilayers, nucleic acids — carries out a functional program specified by the sequence and environment.
Chapter 2: Proteins and Enzymes
2.1 Structure Hierarchy
Primary structure is the amino-acid sequence; secondary structure — α-helix and β-sheet — is stabilized by backbone hydrogen bonds; tertiary structure is the 3D fold; quaternary is the arrangement of subunits. The Ramachandran plot bounds \( \phi, \psi \) dihedral angles to sterically allowed regions.
2.2 Enzyme Kinetics
Michaelis–Menten kinetics models enzyme-catalyzed reactions:
\[ v = \frac{V_{\max}[S]}{K_M + [S]} . \]A Lineweaver–Burk plot linearizes in \( 1/v \) vs \( 1/[S] \); competitive inhibitors raise apparent \( K_M \) without changing \( V_{\max} \); non-competitive lower \( V_{\max} \). Allosteric enzymes with cooperative binding follow Hill kinetics.
2.3 Protein Engineering
Rational design modifies residues to tune stability, affinity, or specificity; directed evolution uses mutagenesis and selection cycles to explore sequence space. Recombinant proteins — insulin, growth factors, monoclonal antibodies — are a pillar of modern therapeutics, produced in bacterial, yeast, or mammalian hosts.
Chapter 3: Carbohydrates, Lipids, and Membranes
3.1 Carbohydrates
Monosaccharides (glucose, fructose), disaccharides, oligosaccharides, and polysaccharides (glycogen, cellulose, glycosaminoglycans) serve as energy stores, structural elements, and information carriers. Surface glycans mediate cell recognition; aberrant glycosylation marks cancer and inflammation.
3.2 Lipids and the Bilayer
Phospholipids self-assemble into bilayers with hydrophilic heads facing water and hydrophobic tails inward. Fluidity is tuned by lipid saturation, chain length, cholesterol content, and temperature. The lateral diffusion coefficient of lipids (\( D \approx 10^{-12}\,\mathrm{m^2/s} \)) and transverse flip-flop timescales (hours) set the substrate for membrane proteins.
3.3 Membrane Proteins
Integral and peripheral membrane proteins implement transport, signalling, adhesion, and catalysis. Ion channels gated by voltage, ligand, or mechanical force generate the electrical activity of excitable cells (BME 284). GPCRs transduce extracellular signals to intracellular second messengers.
Chapter 4: Nucleic Acids and the Central Dogma
4.1 DNA Structure and Replication
Watson–Crick base pairing (A–T, G–C) provides the informational basis for replication. Semi-conservative replication by DNA polymerase at ≈ 1000 bp/s with proofreading yields error rates ≈ 10⁻¹⁰ per base. Chromatin packaging into nucleosomes and higher-order structures regulates accessibility.
4.2 Transcription and Translation
RNA polymerase transcribes DNA to mRNA; in eukaryotes, splicing removes introns. Ribosomes translate mRNA to protein using tRNA adaptors, with the genetic code nearly universal. Post-translational modifications (phosphorylation, glycosylation, ubiquitination) dramatically expand the functional repertoire.
4.3 Gene Regulation
Transcription factors bind promoter and enhancer elements; epigenetic marks (DNA methylation, histone modification) bias expression. Small RNAs (miRNA, siRNA) regulate post-transcriptionally. Synthetic biology exploits these regulatory modules to build engineered circuits in living cells.
Chapter 5: Cell Biology
5.1 Organelles and Cell Types
Nucleus, ER, Golgi, mitochondria, lysosomes, peroxisomes, and cytoskeleton coordinate in a highly organized eukaryotic cell. Cell diversity — epithelial, connective, muscle, nervous — reflects differentiation from stem cells during development. Stem-cell hierarchies underlie tissue homeostasis and regeneration.
5.2 Cell Metabolism
Glycolysis, the citric-acid cycle, and oxidative phosphorylation convert glucose to ATP with ≈ 30–32 ATP per glucose. The proton-motive force across the inner mitochondrial membrane drives ATP synthase following the chemiosmotic theory. Metabolic flux analysis quantifies steady-state fluxes from isotope-labelling data, guiding bioprocess and tissue-engineering design.
5.3 Cell Cycle and Death
The cell cycle — G1, S, G2, M — is regulated by cyclin/CDK complexes with checkpoints at G1/S and G2/M. Apoptosis is a tightly regulated programmed cell death; necrosis, an uncontrolled damage response. Devices that interact with tissues must avoid triggering pathological death modes.
Chapter 6: Systems Biology and Tissue Engineering
6.1 From Parts to Systems
Systems biology models the cell and tissue as networks: metabolic, signalling, gene-regulatory. Ordinary differential equations for enzyme kinetics, flux-balance analysis for steady-state metabolism, and Boolean networks for logical regulation each capture different facets. The engineer’s intuition for feedback, feedforward, robustness, and modularity transfers directly.
6.2 Biomimetic Design
Nature’s design principles — hierarchical structure (bone, nacre), self-assembly (lipid bilayers), self-healing (skin, bone) — guide engineered materials and devices. Mimicking extracellular matrix composition, mechanics, and topography is central to scaffolds that support tissue regeneration.
6.3 Tissue Engineering Principles
The tissue-engineering triad is cells + scaffold + signals. Scaffold design controls porosity, degradation rate, and mechanical compliance. Growth factors and mechanical stimulation (bioreactors) guide differentiation. Oxygen transport — captured by the Thiele modulus
\[ \phi = L\sqrt{\frac{V_{\max}/K_M}{D_{O_2}}} \]— limits scaffold thickness to the ≈ 200 µm diffusion range, motivating vascularization strategies (pre-vascularization, microfluidic scaffolds, angiogenic factor release).
6.4 Looking Forward
Gene editing (CRISPR-Cas9), mRNA therapeutics, organoids, and engineered living materials are reshaping the interface between biology and engineering. A quantitative biology foundation — the aim of this course — is the durable skill that lets a biomedical engineer contribute across whatever specific technologies dominate the field a decade from now.
