THESIS
2022
1 online resource (xii, 86 pages) : illustrations (some color)
Abstract
Membraneless organelles (MLOs) are cellular compartments that, along with membrane-bound
organelles, serve to regulate biochemical processes in a highly crowded and heterogeneous
intracellular environment. Mounting evidence suggest that these membraneless condensates
are formed via liquid-liquid phase separation, with intrinsically disordered proteins (IDPs)
recognized as a major component that dictates their assembly and properties. While they are
recognized as a functional core of many cellular functions, specific aspects regarding their
dynamics, material state transitions, and physicochemical principles influencing their functions
remain largely unexplored. Complex cellular environment makes it challenging to address
these questions and necessitates development of in vitro reduction...[
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Membraneless organelles (MLOs) are cellular compartments that, along with membrane-bound
organelles, serve to regulate biochemical processes in a highly crowded and heterogeneous
intracellular environment. Mounting evidence suggest that these membraneless condensates
are formed via liquid-liquid phase separation, with intrinsically disordered proteins (IDPs)
recognized as a major component that dictates their assembly and properties. While they are
recognized as a functional core of many cellular functions, specific aspects regarding their
dynamics, material state transitions, and physicochemical principles influencing their functions
remain largely unexplored. Complex cellular environment makes it challenging to address
these questions and necessitates development of in vitro reductionist approaches, that
recapitulate basic biological features of MLOs in a minimalistic way, to gain deeper
understanding of biological phase separation.
Here, we evaluated IDP-inspired polymer-oligopeptide hybrid (IPH) as a model artificial
membraneless organelle (aMLO) and quantitatively explored some relevant physicochemical
properties, such as internal dynamics, material properties, sequestration of molecules, and the
capability to perform enzymatic reactions. Experimental evaluations revealed that this aMLO
system exhibits desirable biomimetic characteristics and can recapitulate higher-order
complexity of biological MLOs. In addition, this biomimetic system can incorporate both
simple and multiplex biomimetic functionalities, overall rendering it useful as a study platform
for further elucidation of unknown aspects of biological MLOs and as a synthetic system that
can harness novel functionalities with application in synthetic biology and metabolic
engineering.
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