Modeling transcriptional regulation of the cell cycle using a novel cybernetic-inspired approach
Biophys J. 2023 Dec 15:S0006-3495(23)04148-6. doi: 10.1016/j.bpj.2023.12.010. Online ahead of print.ABSTRACTQuantitative understanding of cellular processes, such as cell cycle and differentiation, is impeded by various forms of complexity ranging from myriad molecular players and their multilevel regulatory interactions, cellular evolution with multiple intermediate stages, lack of elucidation of cause-effect relationships among the many system players, and the computational complexity associated with the profusion of variables and parameters. In this paper, we present a modeling framework based on the cybernetic concept ...
Source: Biophysical Journal - December 16, 2023 Category: Physics Authors: Rubesh Raja Sana Khanum Lina Aboulmouna Mano R Maurya Shakti Gupta Shankar Subramaniam Doraiswami Ramkrishna Source Type: research
Computational simulations of Bispecific T-Cell Engagers by a Multiscale Model
Biophys J. 2023 Dec 14:S0006-3495(23)04150-4. doi: 10.1016/j.bpj.2023.12.012. Online ahead of print.ABSTRACTThe use of bispecific antibodies as T cell engagers can bypass the normal TCR-MHC interaction, redirect the cytotoxic activity of T-cells, and lead to highly efficient tumor cell killing. However, this immunotherapy also causes significant on-target off-tumor toxicologic effects, especially when it is used to treat solid tumors. In order to avoid these adverse events, it is necessary to understand the fundamental mechanisms involved in the physical process of T cell engagement. We developed a multiscale computational...
Source: Biophysical Journal - December 16, 2023 Category: Physics Authors: Zhaoqian Su Steven C Almo Yinghao Wu Source Type: research
Data-driven prediction of α < sub > IIb < /sub > β < sub > 3 < /sub > integrin activation pathways using nonlinear manifold learning and deep generative modeling
Biophys J. 2023 Dec 14:S0006-3495(23)04129-2. doi: 10.1016/j.bpj.2023.12.009. Online ahead of print.ABSTRACTThe integrin heterodimer is a transmembrane protein critical for driving cellular process and is a therapeutic target in the treatment of multiple diseases linked to its malfunction. Activation of integrin involves conformational transitions between bent and extended states. Some of the conformations that are intermediate between bent and extended states of the heterodimer have been experimentally characterized, but the full activation pathways remain unresolved both experimentally due to their transient nature and c...
Source: Biophysical Journal - December 15, 2023 Category: Physics Authors: Siva Dasetty Tamara C Bidone Andrew L Ferguson Source Type: research
MscS inactivation and recovery are slow voltage-dependent processes sensitive to interactions with lipids
Biophys J. 2023 Dec 13:S0006-3495(23)04127-9. doi: 10.1016/j.bpj.2023.12.007. Online ahead of print.ABSTRACTMechanosensitive channel MscS, the major bacterial osmolyte release valve, shows a characteristic adaptive behavior. With a sharp onset of activating tension, the channel population readily opens, but under prolonged action of moderate tension, it inactivates. The inactivated state is non-conductive and tension-insensitive, which suggests that the gate gets uncoupled from the lipid-facing domains. Because the distinct opening and inactivation transitions are both driven from the closed state by tension transmitted th...
Source: Biophysical Journal - December 15, 2023 Category: Physics Authors: Madolyn Britt Elissa Moller Joseph Maramba Andriy Anishkin Sergei Sukharev Source Type: research
Structure-function relationships in the nasal cavity of Arctic and subtropical seals
Biophys J. 2023 Nov 29:S0006-3495(23)00712-9. doi: 10.1016/j.bpj.2023.11.012. Online ahead of print.ABSTRACTThe heating and moistening of inhaled air, and the cooling and moisture removal from exhaled air, are crucial for the survival of animals under severe environmental conditions. Arctic mammals have evolved specific adaptive mechanisms to retain warmth and water and restrict heat loss during breathing. Here, the role of the porous turbinates of the nasal cavities of Arctic and subtropical seals is studied with this in mind. Mass and energy balance equations are used to compute the time-dependent temperature and water v...
Source: Biophysical Journal - December 15, 2023 Category: Physics Authors: Hyejeong L Cheon Signe Kjelstrup Nataliya Kizilova Eirik G Flekk øy Matthew J Mason Lars P Folkow Source Type: research
