Molecular memory in biological networks: mathematical definition and dynamical fundamentals

FEDERICO SEVLEVER; ALEJANDRA C VENTURA

Jornada; Primeras Jornadas Virtuales SAB 2020; 2020

Sociedad Argentina de Biofísica

Cell signaling pathways arenetworks of chemical interactions between biomolecules inside a cell. Theirfunction is to sense chemical signals in the environment and trigger anappropriate response. The responses are diverse: could be synthesis or degradationof proteins, opening of ion channels, cellular differentiation, cell death, andmany others. Some of these pathways canremember past stimuli, and this feature implies that they respond to a newstimulus differently depending on their history. One general definition ofmemory is the persistence of a response through time, after the stimulus hasended. In cell signaling pathways, memory’s hardware are the biomoleculesinvolved. They can trigger a different response from the original one to asecond stimulus, due to a different state or initial position of the network. Thishappens, for example, in bistable systems, where the final state depends on theinitial condition and a first stimulus can move the system irreversibly fromone stable state to the other.A possible measure ofmemory in a network can be the difference in the temporal response with andwithout a previous stimulation. Our work focuses on the mathematical definitionof a memory from this perspective, the proposal of an estimator and its test.We computationally integrate the dynamics of every possible 3-node network (16038in total), for 10000 parameter sets each one. We measure memory in each case,and identify network topologies that robustly lead to memory in the network. Weclassify those topologies, finding that bistability is not the only path toobtain memory.