CH391L/S13/Mechanosensing

Introduction

Mechanosensing refers to the ability of an organism to respond to changes in mechanical force on them or their environment. The mechanical stress can be in a variety of forms:

• Hydrostatic pressure, as in the case of deep ocean environments
• Fluid shear stress, as in the case of blood flowing through veins
• Direct force, as in the case of body weight on a bone
• Osmotic pressure, resulting from a difference in solute concentrations across a semi-permeable membrane

High hydrostatic pressure (HHP) can cause dissociation of multimeric proteins, shifts in reaction equilibria, decreased membrane fluidity, and even unfolding of monomeric proteins in extreme cases (reviewed in [1]. In some cases, changes in mechanical stress result in differential gene expression driven by mechanosensitive promoters or repressors. Genes that have increased expression might include cold- and heat-shock and other stress response proteins, barostable polymerases[2], or membrane proteins [add reference]. Down-regulated genes might include nutrient transporters [Mal operan ref]. In other cases, porin proteins which provide ion diffusion pathways are opened in response to osmotic stress across the membrane.

The first pressure-responsive gene was found in 1989 [3] in a deep-ocean bacterium, Photobacterium profundum strain SS9. The gene encodes for OmpH, a large transmembrane protein which is involved in nutrient uptake. Later work found that the operon also contained two outer membrane proteins, OmpL [include ref] (induced at lower pressures ~1atm) and OmpI [include ref] (induced at much higher pressures ~400atm). These pressure inducible genes were found to be essential for survival under HHP growth conditions[include a ref].

iGEM Connection

There is a brief mention of an idea regarding mechanosensing as an earthquake sensor in the notebook section for the 2012 Baskent University team, but it seems that they chose to pursue a different idea related to quorum sensing.

2010 MIT

In one of their projects, this team focused on engineering pressure sensitive promoters in mammalian cells. They were interested in using pressure as a way to control formation of biomaterials, with a goal of being able to engineer tissues and organs. Specifically, they created a touch pad which would form bone after a pressure change input. They first characterized fluid shear stress responsive promoters and used these to create a genetic toggle switch sensitive to pressure changes. Their touch pad contained human endothelial kidney (HEK) cells with production Bone Morphogenic Protein 2 (BMP2) under control of the pressure sensitive toggle switch, along with undifferentiated stem cells. When pressure is applied, BMP2 production turns on and causes the production of bone tissue via the differentiated stem cells.

2008 Tokyo Tech

Future Directions

It's worth noting that extremely high pressure is gaining popularity as a way to pasteurize foods without heat treatment[4]. The high pressure takes less of a toll on the quality of the food products than heat, but can be just as effective at killing microorganisms. It will be interesting to see if baro-resistant organisms arise from this trend.

References

1. Morozkina EV, Slutskaia ES, Fedorova TV, Tugaĭ TI, Golubeva LI, and Koroleva OV. [Extremophilic microorganisms: biochemical adaptation and biotechnological application (review)]. Prikl Biokhim Mikrobiol. 2010 Jan-Feb;46(1):5-20.
2. Nakasone K, Ikegami A, Fujii S, Kato C, and Horikoshi K. Isolation and piezoresponse of the rpoA gene encoding the RNA polymerase alpha subunit from the deep-sea piezophilic bacterium Shewanella violacea. FEMS Microbiol Lett. 2000 Dec 15;193(2):261-8. DOI:10.1111/j.1574-6968.2000.tb09434.x |
3. Bartlett D, Wright M, Yayanos AA, and Silverman M. Isolation of a gene regulated by hydrostatic pressure in a deep-sea bacterium. Nature. 1989 Nov 30;342(6249):572-4. DOI:10.1038/342572a0 |

   First discovery of pressure-regulated gene