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Crowding Effects on the Formation and Maintenance of Nuclear Bodies: Insights from Molecular-Dynamics Simulations of Simple Spherical Model Particles

Title
Crowding Effects on the Formation and Maintenance of Nuclear Bodies: Insights from Molecular-Dynamics Simulations of Simple Spherical Model Particles
Author
조은진
Keywords
CHROMATIN DOMAINS; REACTION-RATES; CAJAL BODIES; CELL; DIFFUSION; ASSOCIATION; MACROMOLECULES; ORGANIZATION; PROTEINS; DENSITY
Issue Date
2012-08
Publisher
Elsevier Science B.V., Amsterdam
Citation
Biophysical journal, 2012, 103(3), P.424-433
Abstract
The physics of structure formation and maintenance of nuclear bodies (NBs), such as nucleoli, Cajal bodies, promyelocytic leukemia bodies, and speckles, in a crowded nuclear environment remains largely unknown. We investigate the role of macromolecular crowding in the formation and maintenance of NBs using computer simulations of a simple spherical model, called Lennard-Jones (LJ) particles. LJ particles form a one-phase, dilute fluid when the intermolecular interaction is weaker than a critical value, above which they phase separate and form a condensed domain. We find that when volume-exclusive crowders exist in significant concentrations, domain formation is induced even for weaker intermolecular interactions, and the effect is more pronounced with increasing crowder concentration. Simulation results show that a previous experimental finding that promyelocytic leukemia bodies disappear in the less-crowded condition and reassemble in the normal crowded condition can be interpreted as a consequence of the increased intermolecular interactions between NB proteins due to crowding. Based on further analysis of the simulation results, we discuss the acceleration of macromolecular associations that occur within NBs, and the delay of diffusive transport of macromolecules within and out of NBs when the crowder concentration increases. This study suggests that in a polydisperse nuclear environment that is enriched with a variety of macromolecules, macromolecular crowding not only plays an important role in the formation and maintenance of NBs, but also may perform some regulatory functions in response to alterations in the crowding conditions.
URI
http://www.cell.com/biophysj/fulltext/S0006-3495(12)00778-3http://hdl.handle.net/20.500.11754/48898
ISSN
0006-3495
DOI
10.1016/j.bpj.2012.07.007
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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