title: Stochastic modelling suggests that an elevated superoxide anion - hydrogen peroxide ratio can drive extravascular phagocyte transmigration by lamellipodium formation.
abstract: Chemotaxis, integrates diverse intra- and inter-cellular molecular processes into a purposeful patho-physiological response; the operatic rules of which, remain speculative. Here, I surmise, that superoxide anion induced directional motility, in a responding cell, results from a quasi pathway between the stimulus, surrounding interstitium, and its biochemical repertoire. The epochal event in the mounting of an inflammatory response, is the extravascular transmigration of a phagocyte competent cell towards the site of injury, secondary to the development of a lamellipodium. This stochastic-to-markovian process conversion, is initiated by the cytosolic-ROS of the damaged cell, but is maintained by the inverse association of a de novo generated pool of self-sustaining superoxide anions and sub-critical hydrogen peroxide levels. Whilst, the exponential rise of O2(.-) is secondary to the focal accumulation of higher order lipid raft-Rac1/2-actin oligomers; O2(.-) mediated inactivation and redistribution of ECSOD, accounts for the minimal concentration of H2O2 that the phagocyte experiences. The net result of this reciprocal association between ROS/ RNS members, is the prolonged perturbation and remodeling of the cytoskeleton and plasma membrane, a prelude to chemotactic migration. The manuscript also describes the significance of stochastic modeling, in the testing of plausible molecular hypotheses of observable phenomena in complex biological systems.
authors.affiliation: Department of Biochemistry, Dr. Baba Saheb Ambedkar Medical College & Hospital, Government of NCT Delhi, Sector - 6, Rohini, Delhi 110085, India; Mathematical and Computational Biology, Information Technology Research Academy (ITRA), Media Lab Asia, 2nd Floor, Block 2, C-DOT Campus, Mehrauli, New Delhi 110030, India; School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi 110067, India. Electronic address: siddhartha_kundu@yahoo.co.in.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Kundu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002633:Chemotaxis; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010586:Phagocytes / Q000166:cytology* / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D012044:Regression Analysis; D013269:Stochastic Processes; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D006861:Hydrogen Peroxide
keywords: Actin; Chemotaxis; Free radicals; Lipid raft; Stochastic model