Understanding the molecular basis for mechanotransduction
In cells and tissues, the integration and propagation of mechanical signals is facilitated by the activity of molecular machines; small groups of proteins that detect and respond to mechanical stimuli by transferring physical forces to other cellular components, or facilitating their conversion to biochemical signals.
At MBI, we are exploring mechano-transduction though four major research programs: molecular, cellular, tissue, and through technological innovations.
The information obtained during this process, which is known as mechanosensing, helps in cellular decision making.This is particularly important during development, when stem cells are differentiating to become specific cell types, and during wound healing or tissue repair.
Cells can measure the stiffness of the surface on which they are growing and they can detect and respond to tension from neighboring cells within a tissue. Understanding how individual cells and proteins contribute to the mechanotransduction of physical force, is a major focus in the research conducted at the MBI. Dissecting the nanoscale architecture of various molecular machines involves the manipulation of specific cellular components, and at times, single proteins or specific protein domains. We can then monitor any subsequent effects.
Crucial to these efforts is the ability to control and modify the physical parameters of the cellular microenvironment. This means growing cells on substrates of a specific stiffness, pattern or shape. The effect of any molecular manipulation must then be monitored by quantifying the forces generated by cells or individual proteins, or visualizing the effects using super-resolution microscopy techniques.
- Yan J, Yu Y, Kang JW, Tam ZY, Xu S, Fong ELS, Singh SP, Song Z, Tucker-Kellogg L, So PTC, and Yu H. Development of a classification model for non-alcoholic steatohepatitis (NASH) using confocal Raman micro-spectroscopy. J Biophotonics 2017;. [PMID: 28635128]
- Wang Y, Nagarajan M, Uhler C, and Shivashankar GV. Orientation and Repositioning of Chromosomes Correlate with Cell Geometry-dependent Gene Expression. Mol. Biol. Cell 2017;. [PMID: 28615317]
- Sethi K, Cram EJ, and Zaidel-Bar R. Stretch-induced actomyosin contraction in epithelial tubes: Mechanotransduction pathways for tubular homeostasis. Semin. Cell Dev. Biol. 2017;. [PMID: 28610943]
- Dasgupta S, Auth T, and Gompper G. Nano- and Microparticles at Fluid and Biological Interfaces. J Phys Condens Matter 2017;. [PMID: 28608781]
- Hu B, Leow WR, Amini S, Nai B, Zhang X, Liu Z, Cai P, Li Z, Wu Y, Miserez A, Lim CT, and Chen X. Orientational Coupling Locally Orchestrates a Cell Migration Pattern for Re-Epithelialization. Adv. Mater. Weinheim 2017;. [PMID: 28585393]
- Ramanujam R, Low TYF, Lim YW, and Motegi F. Forceful patterning in mouse preimplantation embryos. Semin. Cell Dev. Biol. 2017;. [PMID: 28577924]
- Hara Y. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue. Dev. Growth Differ. 2017;. [PMID: 28573735]
- Geldert A, Kenry , Zhang X, Zhang H, and Lim CT. Enhancing the sensing specificity of a MoS2 nanosheet-based FRET aptasensor using a surface blocking strategy. Analyst 2017;. [PMID: 28569315]
- Tan SJ, Yeo T, Sukhatme SA, Kong SL, Lim W, and Lim CT. Personalized Treatment Through Detection and Monitoring of Genetic Aberrations in Single Circulating Tumor Cells. Adv. Exp. Med. Biol. 2017; 994:255-273. [PMID: 28560679]
- Wang Y, Jain N, Nagarajan M, Maharana S, Iyer KV, Talwar S, and Shivashankar GV. Coupling between chromosome intermingling and gene regulation during cellular differentiation. Methods 2017;. [PMID: 28554525]
A question of life and death
MBI Scientists reveal a spatial dimension to cell signaling
Basal protrusions stimulate rosette formation during cell intercalation
Actin remodeling drives bile regurgitation during obstructive cholestasis
A molecular rivet for long-range force transmission