The Emergence of Multistationarity in a MAPK Network Model

Abstract

The MAPK network is a principal component of many intracellular signaling modules.В  Multistability (the existence of multiple stable steady states)В  is considered an important property of such systems and its origin is not yetВ  completely understood. Theoretical studies have establishedВ parameter values for multistabilityВ  for manyВ models of MAPK networks.В  Up to nowВ  decidingВ ifВ  a given model of a MAPK networkВ  hasВ  the capacity for multistationarity (the existence of multiple steady states)В required extensive search of theВ  parameter space.В Two simple parameterВ  inequalities will be presented. IfВ В  the firstВ  inequality isВ  satisfied,В  itВ  guarantees multistationarity (and hence the potential for multistability). If theВ  second inequalityВ  is satisfied,В  it guarantees theВ uniqueness of a steady stateВ  (and hence the absence of multistability). TheВ  method also allows for theВ direct computation of the total concentration values such thatВ В  multistationarity occurs.В В  The emergence of multistability in theВ  ERK - MEK - MKP model thatВ В  previously required a delicate numerical effort will be discussed.