Cell Biology (Notes 39)

Final exam

Immanuel Kant

• Scientist explored the question of “what is life??”

• One of the first cell biologists - said life is a “self-organized, self-reproducing process”

  • The functions of a cell emerge by the process of self-organization

How do you reduce entropy in the system,?

• A cell is an island of order in a sea of disorder —> churning of water causes currents in the water known as Benard rolls

  • There is energy being put INTO the system: heat

  • The collective interactions of the water molecules with the addition of thermal energy is creating order

  • These currents of water can be moving clockwise or counterclockwise

  • Energy is important for creating order

How can order also be produced by diffusion and feedback loops?

• Turing patterns: a Turing pattern can be produced if two conditions are met (this is order met in the system)

  • A feedback loop that’s activating

  • An interlocked loop that is expressing an inhibitor that down regulates the loop that’s being activated

• Found also in the cell cycle

• When these chemicals intermix, they can form an interaction product that is white under the correct conditions

• By mixing the chemicals together, there is a very ordered pattern of spots

  • This is a classic Turing pattern - the polka dots

  • This is what Turing predicted would happen under two conditions

    • Short-range activating molecule

    • A fast-diffusing inhibitor (long-range)

    • Needs to be diffusing quickly from its source

    • If you change the stability of the system, that is, the concentration of the molecules locally within the system, a different pattern will emerge

  • If there is instability in the concentration of molecules in the field of view, there is an instability emerging

Diffusion Instability

• Don’t have constant concentration of molecules due to stochastic fluctuations in the diffusion of the molecules

• Go from a polka dot pattern to a zebra like pattern

Where does order in a cell come from?

1. Order in a cell can result from stereo-specific molecular interactions that form a STATIC, stable structure at thermodynamic equilibrium

   1. Self-Assembly

   2. Where cells encounter viruses - the virion is surrounded by proteins that self-assemble (they interlock with each other and fit together one way)

   3. Each subunit adds to the coat of the viral particle

2. Molecular interactions that form dynamic steady-state structures and are accompanied by a dissipation of energy

   1. Self-Organization

   2. Golgi

   3. Microtubules growing and shrinking - examples of self-organization

   4. Molecule interactions that form dynamic, steady-state structures and accompanied by a dissipation of energy

      1. GTP is formed and adds onto the microtubule

      2. If you want to disassemble the microtubule, you have to hydrolyze the GTP

      3. There is always energy required to keep this system in a steady state

      4. Think of the mitotic spindle as the self-organized structure —> spindle has great order to it

         1. That is all forming due to the actions of motor proteins

         2. Microtubules are sliding past each other and pushing the spindle apart and organizing the two spindles relative to each other

         3. Those motor proteins are dissipating energy to form a spindle

         4. Can form spindle without centrosome, like in plant cells

   5. DNA, not because of what it encodes, but its very structure, can allow for molecular structure that can lead to higher-order structure and segregation

      1. There’s temporal organization superimposed over spatial organization

Erwin Schrödinger

• Organism (cell) ’s astonishing gift of concentrating a “stream of order” on itself

• This is what life is about - ability to concentrate order

Pollard’s Essential Tasks of Reductionism in Cell Biology

• How much do we really know about the cell?

• If we thought about any phenomenon a cell executes, what do we really need to know to fully understand what we’re observing?

• There are ten things you need to know:

  • Define a question - what are you looking at?

  • How does a cell carry out a specific process?

• Can identify molecular constituents of a cell

  • Can know the structure of a lot of molecules

  • We know where a lot of molecules interact with a lot of other molecules and what pathways

• What we lack:

  • Knowing what’s the in vivo concentration of the molecules in the cell

  • Determine the structure of atomic resolution

  • Determine the rate constant and the equilibrium constant in vivo

  • We don’t have a good chemical grasp of what we know about in the cell

  • Challenging how we understand the physiology of the cell

• If we know what’s going on in the cell, can formulate quantitative model of system behavior

  • Cell should behave according to the model

Bacterial Cell Motility

• Can understand that process fully

• Can understand some part of that list but can’t know the list completely

Reductionism

• Take a complex picture of a cell and break it down into all these parts

• Can do in vitro recombination and see if you can re-capitulate the process

• Have to understand how the entire process is integrated together

  • Many cells are happening simultaneously to know how a cell will grow

  • Have to observe all the systems simultaneously

Systems Biology/Network Biology

• Can collect 50,000 data points at one time and can understand how all those data points connect to one another