Wouter-Jan Rappel UCSD.ppt

Establishing direction during chemotaxis in eukaryotic cells: What can theoretical models tell us? Ability to respond to spatial and temporal gradients of chemoattractants/repellants Present in many eukaryotic cell types Gradients determine direction of motion Examples Wound healing Embryogenesis Neuronal patterning Angiogenesis What Is Dicty? Unicellular amoeba ( ~ 10 mm). Live as separate cells on forest floor; feed on bacteria. Upon starvation cells interact by chemical signals, adhesion, etc. and aggregate (50,000 cells). Differentiate into 20% stalk and 80% spore cells. Form slug (~ mm) and fruiting body. Lifecycle Why study chemotaxis in Dicty? Cells are chemotactic to cAMP cAMP binds to cell membrane via receptor CAR1 (~5,000 molecules). cAMP waves in developing populations Uniform stimulus Relay model for Dicty We propose: cGMP is a good candidate No direct evidence against cGMP Produced rapidly after cAMP stimulus Relay model Our model Uniform pulse of cAMP Asymmetric pulse Asymmetric pulse, cont. Pulse from the left (front) followed by pulse fromthe right (back) Timing experiment uses laminar flow Result from the numerical model: Some more remarks Summary Model can produce significant asymmetry within a few seconds Requires rapidly diffusing internal messenger Likely candidate: cGMP (mutant data) Specific predictions can verify model Future work Perform proposed dual injection experiment Verify prediction for mutant experiments Extend model past initial response (include adaptation) Develop different numerical techniques (phase-field method) Sensitivity to parameter values Response to pulse from micro capillary Asymmetric response of PH domain proteins also found in Neutrophils Changed five parameters ( ) two or five fold up and down Investigated amplification ratio for 243 combinations of parameter values cAMP micro capillary near right upper corner. Images taken every 5 seconds. From C.A. Parent and P.N. Devreotes