TY - JOUR
T1 - Deciphering the Thermal Stability of Bacteriophage MS2-Derived Virus-like Particle and Its Engineered Variant
AU - Vishwakarma, Pragati
AU - Puri, Sarita
AU - Banerjee, Manidipa
AU - Chang, Chia Yu
AU - Chang, Chia Ching
AU - Chaudhuri, Tapan K.
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/8/12
Y1 - 2024/8/12
N2 - RNA bacteriophage MS2-derived virus-like particles (VLPs) have been widely used in biomedical research as model systems to study virus assembly, structure-function relationships, vaccine development, and drug delivery. Considering the diverse utility of these VLPs, a systemic engineering approach has been utilized to generate smaller particles with optimal serum stability and tissue penetrance. Additionally, it is crucial to demonstrate the overall stability of these mini MS2 VLPs, ensuring cargo protection until they reach their target cell/organ. However, no detailed analysis of the thermal stability and heat-induced disassembly of MS2 VLPs has yet been attempted. In this work, we investigated the thermal stability of both wild-type (WT) MS2 VLP and its “mini” variant containing S37P mutation (mini MS2 VLP). The mini MS2 VLP exhibits a higher capsid melting temperature (Tm) when compared to its WT MS2 VLP counterpart, possibly attributed to its smaller interdimer angle. Our study presents that the thermal unfolding of MS2 VLPs follows a sequential process involving particle destabilization, nucleic acid exposure/melting, and disassembly of VLP. This observation underscores the disruption of cooperative intersubunit interactions and protein-nucleic acid interactions, shedding light on the mechanism of heat-induced VLP disassembly.
AB - RNA bacteriophage MS2-derived virus-like particles (VLPs) have been widely used in biomedical research as model systems to study virus assembly, structure-function relationships, vaccine development, and drug delivery. Considering the diverse utility of these VLPs, a systemic engineering approach has been utilized to generate smaller particles with optimal serum stability and tissue penetrance. Additionally, it is crucial to demonstrate the overall stability of these mini MS2 VLPs, ensuring cargo protection until they reach their target cell/organ. However, no detailed analysis of the thermal stability and heat-induced disassembly of MS2 VLPs has yet been attempted. In this work, we investigated the thermal stability of both wild-type (WT) MS2 VLP and its “mini” variant containing S37P mutation (mini MS2 VLP). The mini MS2 VLP exhibits a higher capsid melting temperature (Tm) when compared to its WT MS2 VLP counterpart, possibly attributed to its smaller interdimer angle. Our study presents that the thermal unfolding of MS2 VLPs follows a sequential process involving particle destabilization, nucleic acid exposure/melting, and disassembly of VLP. This observation underscores the disruption of cooperative intersubunit interactions and protein-nucleic acid interactions, shedding light on the mechanism of heat-induced VLP disassembly.
KW - bacteriophage MS2
KW - cooperative interactions
KW - heat-induced capsid disassembly
KW - protein denaturation
KW - virus-like particle
UR - http://www.scopus.com/inward/record.url?scp=85197769722&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.4c00770
DO - 10.1021/acsbiomaterials.4c00770
M3 - Article
AN - SCOPUS:85197769722
SN - 2373-9878
VL - 10
SP - 4812
EP - 4822
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
IS - 8
ER -
