🔬Biophysics Unit 2 – Thermodynamics in Biological Systems

Key Concepts and Definitions

• Thermodynamics studies the relationships between heat, energy, and work in a system
• Biophysics applies physical principles and methods to understand biological systems and processes
• Energy is the capacity to do work or cause change and exists in various forms (kinetic, potential, thermal, chemical)
• Heat is the transfer of thermal energy between systems or within a system
• Entropy measures the degree of disorder or randomness in a system and always increases in spontaneous processes
• Gibbs free energy ($\Delta G$) predicts the spontaneity of a reaction at constant temperature and pressure
  • Reactions with negative $\Delta G$ are spontaneous and release energy
  • Reactions with positive $\Delta G$ are non-spontaneous and require energy input
• Chemical equilibrium occurs when the rates of forward and reverse reactions are equal, and the concentrations of reactants and products remain constant

Laws of Thermodynamics in Biology

• The First Law of Thermodynamics states that energy cannot be created or destroyed, only converted from one form to another
  • In biological systems, energy is conserved in chemical bonds and released through metabolic reactions
• The Second Law of Thermodynamics states that the total entropy of an isolated system always increases over time
  • Living organisms maintain a state of low entropy by consuming energy and releasing heat and waste products
• The Third Law of Thermodynamics states that the entropy of a perfect crystal at absolute zero is zero
  • This law has limited applications in biology since living systems do not operate at absolute zero temperatures
• The Zeroth Law of Thermodynamics defines thermal equilibrium and states that if two systems are in thermal equilibrium with a third system, they are also in thermal equilibrium with each other
• Biological systems obey the laws of thermodynamics, which govern energy transformations and the direction of spontaneous processes

Energy Transfer in Biological Systems

• Energy is transferred between molecules through chemical reactions, such as the breaking and forming of chemical bonds
• Photosynthesis converts light energy into chemical energy stored in glucose molecules, which are later used to power cellular processes
• Cellular respiration releases the chemical energy stored in glucose through a series of enzymatic reactions, ultimately producing ATP
• ATP (adenosine triphosphate) is the primary energy currency in biological systems, used to power various cellular processes
  • ATP stores energy in its high-energy phosphate bonds, which are broken to release energy for work
• Energy can also be transferred through mechanical work, such as the contraction of muscles or the movement of flagella
• Heat is released as a byproduct of many cellular processes, and organisms have evolved mechanisms to regulate body temperature (thermoregulation)
• Electron transport chains in mitochondria and chloroplasts couple the transfer of electrons to the pumping of protons across membranes, creating electrochemical gradients used for ATP synthesis

Entropy and Living Organisms

• Living organisms are highly ordered systems with low entropy compared to their surroundings
• To maintain their low entropy state, organisms must constantly consume energy and export entropy in the form of heat and waste products
• The Second Law of Thermodynamics dictates that the total entropy of an isolated system always increases over time
  • Living organisms are open systems that exchange matter and energy with their surroundings, allowing them to maintain a low entropy state
• Entropy increases during spontaneous processes, such as the diffusion of molecules across a concentration gradient or the unfolding of proteins
• Organisms use energy-consuming processes, such as active transport and protein folding, to counteract the natural increase in entropy
• The organization and complexity of life are maintained through the constant input of energy and the dissipation of entropy into the environment

Gibbs Free Energy and Biochemical Reactions

• Gibbs free energy ($\Delta G$) is a thermodynamic quantity that predicts the spontaneity of a reaction at constant temperature and pressure
  • Reactions with negative $\Delta G$ are spontaneous and release energy, while reactions with positive $\Delta G$ are non-spontaneous and require energy input
• The change in Gibbs free energy for a reaction is given by the equation: $\Delta G = \Delta H - T\Delta S$, where $\Delta H$ is the change in enthalpy, $T$ is the absolute temperature, and $\Delta S$ is the change in entropy
• In biochemical reactions, enzymes lower the activation energy barrier, allowing reactions to proceed more quickly without changing the overall $\Delta G$ of the reaction
• Coupled reactions, such as the hydrolysis of ATP coupled to the synthesis of biomolecules, allow thermodynamically unfavorable reactions to proceed by linking them to favorable ones
• The equilibrium constant (K) of a reaction is related to the standard Gibbs free energy change ($\Delta G^\circ$) by the equation: $\Delta G^\circ = -RT \ln K$, where $R$ is the gas constant and $T$ is the absolute temperature
• Gibbs free energy calculations are used to predict the direction and spontaneity of biochemical reactions, such as those involved in metabolism, signal transduction, and gene regulation

Membrane Potentials and Ion Gradients

• Biological membranes are selectively permeable barriers that separate the interior of a cell from its environment
• Ion gradients across membranes create electrical potentials, known as membrane potentials, which are crucial for various cellular processes
  • The resting membrane potential of a cell is determined by the unequal distribution of ions (primarily Na+, K+, and Cl-) across the membrane
• The concentration gradients of ions are maintained by active transport proteins, such as the Na+/K+ ATPase, which use energy from ATP hydrolysis to pump ions against their concentration gradients
• Passive transport processes, such as facilitated diffusion and ion channels, allow ions to move down their concentration gradients without energy input
• The Nernst equation relates the equilibrium potential of an ion to its concentration gradient across a membrane: $E = \frac{RT}{zF} \ln \frac{[ion]_{out}}{[ion]_{in}}$, where $E$ is the equilibrium potential, $R$ is the gas constant, $T$ is the absolute temperature, $z$ is the ion's charge, $F$ is Faraday's constant, and $[ion]$ is the ion concentration
• The Goldman-Hodgkin-Katz equation extends the Nernst equation to account for the permeability of a membrane to multiple ions, providing a more accurate prediction of the resting membrane potential
• Membrane potentials and ion gradients are essential for processes such as neurotransmission, muscle contraction, and the generation of action potentials

Metabolic Processes and ATP Synthesis

• Metabolism encompasses the sum of all chemical reactions in a living organism, including both catabolic (energy-releasing) and anabolic (energy-consuming) processes
• Catabolic pathways, such as glycolysis and the citric acid cycle, break down complex molecules to release energy in the form of ATP and reduced electron carriers (NADH and FADH2)
• Anabolic pathways, such as the synthesis of proteins, lipids, and nucleic acids, require energy input from ATP and reduced electron carriers to build complex molecules from simpler precursors
• ATP is synthesized primarily through the process of oxidative phosphorylation, which couples the transfer of electrons from reduced electron carriers to the pumping of protons across the inner mitochondrial membrane
  • The resulting proton gradient is used to drive the enzyme ATP synthase, which catalyzes the phosphorylation of ADP to form ATP
• Substrate-level phosphorylation is another mechanism of ATP synthesis, in which a high-energy phosphate group is directly transferred from a substrate to ADP (e.g., during glycolysis)
• The efficiency of ATP production is determined by the number of protons pumped per electron transferred and the number of ATP molecules synthesized per proton that flows back through ATP synthase
• Metabolic regulation ensures that the rates of catabolic and anabolic processes are balanced to maintain energy homeostasis in the cell
  • Regulation occurs through allosteric control of enzymes, feedback inhibition, and control of gene expression

Applications in Molecular Biology and Biotechnology

• Thermodynamic principles are applied in the design and optimization of PCR (polymerase chain reaction) assays, which rely on temperature cycling to amplify specific DNA sequences
• The stability of nucleic acid secondary structures, such as hairpins and stem-loops, can be predicted using thermodynamic calculations based on the Gibbs free energy of base-pairing interactions
• Protein folding and stability are influenced by thermodynamic factors, such as the hydrophobic effect and the formation of hydrogen bonds and disulfide bridges
  • Understanding these factors is crucial for protein engineering and the design of stable, functional proteins for biotechnological applications
• Metabolic engineering involves the modification of metabolic pathways to optimize the production of desired compounds, such as biofuels, pharmaceuticals, and industrial chemicals
  • Thermodynamic analysis is used to identify bottlenecks and optimize the efficiency of engineered pathways
• Bioenergetics, the study of energy transformations in living systems, is crucial for understanding the growth and productivity of organisms used in biotechnology, such as bioreactors and fermentation processes
• The development of biosensors and bioelectronic devices relies on understanding the thermodynamics of biomolecular interactions and electron transfer processes
• Thermodynamic principles are applied in the design of drug delivery systems, such as liposomes and nanoparticles, to optimize drug stability, release kinetics, and targeting efficiency