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 a host of problems, including dissociation of multimeric proteins, shifts in reaction equilibria, loss of membrane integrity, and protein denaturation (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[2], barostable polymerases[3], or membrane proteins [add reference]. Down-regulated genes might include nutrient transporters[4]. In other cases, porin proteins which provide ion diffusion pathways are opened in response to osmotic stress across the membrane.

Mechanosensing in Prokaryotes

The first pressure-responsive gene in bacteria was found in 1989[5] 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[6] (induced at lower pressures ~1atm) and OmpI[7] (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[1]. 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. Follonier S, Panke S, and Zinn M. Pressure to kill or pressure to boost: a review on the various effects and applications of hydrostatic pressure in bacterial biotechnology. Appl Microbiol Biotechnol. 2012 Mar;93(5):1805-15. DOI:10.1007/s00253-011-3854-6 |
2. Ambily Nath IV and Loka Bharathi PA. Diversity in transcripts and translational pattern of stress proteins in marine extremophiles. Extremophiles. 2011 Mar;15(2):129-53. DOI:10.1007/s00792-010-0348-x |
3. 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 |
4. Sato T, Nakamura Y, Nakashima KK, Kato C, and Horikoshi K. High pressure represses expression of the malB operon in Escherichia coli. FEMS Microbiol Lett. 1996 Jan 1;135(1):111-6. DOI:10.1111/j.1574-6968.1996.tb07974.x |
5. 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

6. Welch TJ and Bartlett DH. Isolation and characterization of the structural gene for OmpL, a pressure-regulated porin-like protein from the deep-sea bacterium Photobacterium species strain SS9. J Bacteriol. 1996 Aug;178(16):5027-31. DOI:10.1128/jb.178.16.5027-5031.1996 |
7. Chi E and Bartlett DH. Use of a reporter gene to follow high-pressure signal transduction in the deep-sea bacterium Photobacterium sp. strain SS9. J Bacteriol. 1993 Dec;175(23):7533-40. DOI:10.1128/jb.175.23.7533-7540.1993 |
8. 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.