1. 1. Using a Lattice Model to Study the Nuclear Pore Complex Samantha Norris Mentors: Meredith Betterton, Loren Hough, Mike Stefferson August 6, 2015
2. 2. What is the Nuclear Pore Complex (NPC)? "NuclearPore crop" by The original uploader was R. S. Shaw at English Wikipedia - Transferred from en.wikipediato Commons.. Licensed under CC BY-SA 2.5 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:NuclearPore_crop.png#/media/File:NuclearPore_crop.png protein Transport factor Strands of nucleoporins with FG sequence repeats (FG nups) Nucleus Cytoplasm
3. 3. What I Did To better understand the diffusion of proteins through the NPC To find the parameters which most significantly affect diffusion Purpose Built Monte-Carlo lattice model from scratch Included particle and polymer lattice moves Tested various sets of parameters
4. 4. Experimental Progress Modelling the NPC with a hydrogel mimic Hydrogel consists of FG-nups in strands Figure: Loren Hough
5. 5. A Lattice Model Monte Carlo method each particle (whether TF or FG) takes random walk around the grid When a TF and FG collide, probability of binding When separating, probability of unbinding
6. 6. A Lattice Model Probability: Probability:
7. 7. A Lattice Model inlet outlet
8. 8. Strand Statistics Movement rules adapted from Haire et. al. Anchored at one point If movement breaks strand in 1 place, rest of strand compensates If movement breaks strand in 2 places, move rejected
9. 9. Strand Statistics Deviation from center # 1 strand, length 200, T = 100,000
10. 10. Strand Statistics Leftmost figure reprinted from "A Monte Carlo Lattice model for Chain Diffusion in Dense Polymer Systems and its Interlocking with Molecular Dynamics Simulation," by K.R. Haire et. al., 2001, Computational and Theoretical Polymer Science
11. 11. Calculating Diffusion Coefficients bindable particles unbindable particles Slope diffusion coefficient
12. 12. Calculating Mean Square Displacement Old Method: Find distance from starting position for each particle at each time steps, average over particles New Method: Same as above, but average over different time origins, doesnt choose starting position preferentially
13. 13. Parameters kon, koff (binding and unbinding probability) Concentration of FG-nups and TFs Gel width TF size
14. 14. = .5 = /10 TF # = 1 Length = 100 Gel width = 50 Conclusion: Lower concentration = Higher diffusion FG %
15. 15. FG conc. = 10% = /10 TF # = 1 Length = 100 Gel width = 100 Conclusion: higher = Higher diffusion
16. 16. FG conc. =10% = 0.5 TF # = 1 Length = 100 Gel width = 100 Conclusion: Significant only when
17. 17. FG radius Conclusion: No effect, requires more study FG conc. = 5% of gel =0.5 = /10 TF # = 1 Length = 100
18. 18. Future Plans Reproduce figures from other papers on diffusion on lattice grid Study the long-time behavior of diffusion Possibly add more complex situations (TFs moving and pushing FGs, etc.)
19. 19. Thank you! REU organizers Meredith Betterton, Loren Hough (mentors) Mike Stefferson (graduate student) Jeff Moore, Adam Lamson, Andrea Egan