From Self-Assembly to Cell Recognition - Lecture 2

Explore the fascinating world of self-assembly and cell recognition in this comprehensive lecture by Daan Frenkel. Delve into the principles of structural and addressable complexity, focusing on DNA-mediated interactions and their role in colloidal self-assembly. Examine the challenges of creating complex DNA-colloid structures and learn about the concept of addressable complexity through the analogy of self-assembling puzzles. Discover how multivalency affects recognition processes in nature and its advantages in biological systems. Investigate the theory and simulations behind multivalent binding, including its applications in cell receptor profiles. Gain insights into the relationship between fever and infection from a molecular perspective. This lecture offers a comprehensive overview of cutting-edge research in soft matter physics and its implications for understanding biological processes.

Eagle's DNA
Self-Assembly -Benjamin Rogers
What kind of functions?
What kind of structures are required?
Example of structures with addressable complexity
1. 'Structural' Complexity through packing lecture 1 2. 'Addressable' Complexity through specific interactions
Specific interactions are needed for particle recognition example DNA-mediated interactions
Early example: DNA recognition
Complementary sequence Single-base mismatched sequence
Oversimplified Explanation of sensitivity: "Cooperativety"
First consider 1 bond: binding free energy of delta f
Key point
Simple theory:
DNA-Mediated Colloidal Self-Assembly
Why is it difficult to make DNA-Colloid structures with hundreds of components?
Addressable Complexity: The Assembly Of Puzzles.
Many Hours Later...
Clearly, we need puzzles that can self-assemble Materials with 'addressable complexity'
Example of Addressably Complex Material
Building Blocks: 32-nucleotide DNA strands
How is it possible to assemble thousands ofdifferent DNA strands?
Simulations: 998 different DNA 'bricks'.
Not Just Cubes:
Structure formation proceed via 'nucleation and growth'
A simple theory Will Jacobs can reproduce the observed structure of the free energy barriers
When DNA bricks 'nucleate' they cannot yet form the compete target structure
Can we go beyond "pure' DNA?
Designing complex, periodic patterns Y. Ke et al., Nature Chemistry 6, 994 2014
Multivalency and Recognition
Consider Limiting Case of Very Strong Bonding No Free Bonds
Multivalent binding in nature:
Multivalent binding - What are the advantages?
The key quantity to optimise is the selectivity a:
Experiments with multivalent polymers:
In reality, cells have a receptor 'profile'.
Interestingly, two very simple rules result:
Comparison theory-simulations
Question: why do we get a fever when we have an infection?
Thank You