LAUSR

A new class of thermally responsive protein based block co-polymers shows tunable hysteresis in their thermal transitions. The sequences encompass intrinsically disordered regions comprising of repeats of Elastin-Like Polypeptides (ELPs). These are interspersed with alpha-helical polyalanine domains. The lower critical solution temperatures (LCSTs) measured along the heating and cooling arms are tunable and can be non-overlapping. The number and type of alanine-rich blocks determine the extent of hysteresis. We have developed a phenomenological model that reproduces the experimentally observed tunable hysteresis for block copolymeric sequences. This requires an imbalance between the strengths of homotypic interactions between alanine-rich regions and ELP repeats. Additionally, the ELPs and alanine-rich regions have to be immiscible with one another. These features engender micro-phase separation whereby the block copolymers form spherical clusters comprising of alanine-rich cores and ELP coronas. Upon raising the temperature above the LCST, the clusters are drawn to one another by favorable interactions among ELPs and these clusters further network via domain swapping of alanine-rich regions. Lowering the temperature below the LCST leads to dispersion of the clusters by weakening of homotypic interactions between ELPs. However, the domain swapped states persist and this maintains the physical networking of clusters thus giving rise to hysteresis. Domain swapping and the persistence of this state below the LCST are governed by the energy gap between the homotypic interactions of ELPs vis-a-vis alanine-rich regions. Our findings have direct bearing on the de novo design of responsive materials based on IDPs, where tunable hysteresis can be used to encode memory effects, and for understanding the complexities of sequence-encoded phase behavior of archetypal low complexity disordered proteins.