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Polymers and Self Assembly: From Biology to Nanomaterials Poster Session I
14-POS
Board 14
Competition or Forced Collaboration? On the Relationship Between Two Types of Insulin
Amyloid Seed.
Wojciech Dzwolak
1,2
, Weronika Surmacz-Chwedoruk
2,3
, Viktoria Babenko
1
.
1
University of Warsaw, Warsaw, Poland,
2
Polish Academy of Sciences, Warsaw, Poland,
3
Institute of Biotechnology and Antibiotics, Warsaw, Poland.
Cross-seeding of fibrils of bovine insulin (BI) and LysB31-ArgB32 human insulin analog (KR)
induces self-propagating amyloid variants with infrared features inherited from mother seeds.
We have shown recently that when native insulin (BI or KR) is simultaneously seeded with
mixture of equal amounts of both templates (i.e., of separately grown fibrils of BI and KR), the
phenotype of resulting daughter fibrils is as in the case of the purely homologous seeding:
heterologous cotemplates accelerate the fibrillation but do not determine infrared traits of the
daughter amyloid [1]. This implies that fibrillation-promoting and structure-imprinting properties
of heterologous seeds become uncoupled in the presence of homologous seeds. We argue that
explanation of such behavior requires that insulin molecules partly transformed through
interactions with heterologous fibrils are subsequently recruited by homologous seeds. The
selection bias toward homologous daughter amyloid is exceptional: more than 200-fold excess of
heterologous seed is required to imprint its structural phenotype upon mixed seeding. Our study
captures a snapshot of elusive docking interactions in statu nascendi of elongation of amyloid
fibril and suggests that different types of seeds may collaborate in sequential processing of
soluble protein into fibrils. Furthermore, it demostrates that the actual nature of events taking
place upon integration of soluble protein with amyloid tips may be much more complex than is
currently assumed.
[1] W. Surmacz-Chwedoruk, V. Babenko, W. Dzwolak,
J. Phys Chem B.
118 (2014) 13582-
13589