Engineering cellular computations through biophysical design*

It is known that living cells use complex biochemical networks to perform sophisticated computational tasks. Yet, a major question in synthetic and systems biology remains: How are network level computational properties encoded in the biophysics of protein-protein interactions (PPIs)? We address this question by developing a new computational framework relating the thermodynamics of PPIs to network signaling properties in a simplified synthetic biochemical system inspired by the “reader-writer-eraser" signaling paradigm. Our computational framework allows us both to rationally design a desired input-output relation and to identify networks that optimize information transmission (InfoMax). More generally, our work shows that complex computational and information processing tasks can be programmed in cellular signaling circuits by manipulating biophysical parameters.