scholarly journals Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw7243 ◽  
Author(s):  
Runchen Zhao ◽  
Alexandros Afthinos ◽  
Tian Zhu ◽  
Panagiotis Mistriotis ◽  
Yizeng Li ◽  
...  

How cells sense hydraulic pressure and make directional choices in confinement remains elusive. Using trifurcating Ψ-like microchannels of different hydraulic resistances and cross-sectional areas, we discovered that the TRPM7 ion channel is the critical mechanosensor, which directs decision-making of blebbing cells toward channels of lower hydraulic resistance irrespective of their cross-sectional areas. Hydraulic pressure–mediated TRPM7 activation triggers calcium influx and supports a thicker cortical actin meshwork containing an elevated density of myosin-IIA. Cortical actomyosin shields cells against external forces and preferentially directs cell entrance in low resistance channels. Inhibition of TRPM7 function or actomyosin contractility renders cells unable to sense different resistances and alters the decision-making pattern to cross-sectional area–based partition. Cell distribution in microchannels is captured by a mathematical model based on the maximum entropy principle using cortical actin as a key variable. This study demonstrates the unique role of TRPM7 in controlling decision-making and navigating migration in complex microenvironments.

2021 ◽  
pp. 20210290
Author(s):  
Ankita Aggarwal ◽  
Chandan Jyoti Das ◽  
Neena Khanna ◽  
Raju Sharma ◽  
Deep Narayan Srivastava ◽  
...  

Objective: Early detection of peripheral neuropathy is extremely important as leprosy is one of the treatable causes of peripheral neuropathy. The study was undertaken to assess the role of diffusion tensor imaging (DTI) in ulnar neuropathy in leprosy patients. Methods: This was a case–control study including 38 patients (72 nerves) and 5 controls (10 nerves) done between January 2017 and June 2019. Skin biopsy proven cases of leprosy, having symptoms of ulnar neuropathy (proven on nerve conduction study) were included. MRI was performed on a 3 T MR system. Mean cross-sectional area, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of ulnar nerve at cubital tunnel were calculated. Additional ancillary findings and appearance of base sequences were evaluated. Results: Ulnar nerve showed thickening with altered T2W signal in all the affected nerves, having an average cross-sectional area of 0.26 cm2. Low FA with mean of 0.397 ± 0.19 and high ADC with mean of 1.28 ± 0.427 x 10 −3 mm2/s of ulnar nerve in retrocondylar groove was obtained. In the control group, mean cross-sectional area was 0.71cm2 with mean FA and ADC of 0.53 ± 0.088 and 1.03 ± 0.24 x 10 −3 mm2/s respectively. Statistically no significant difference was seen in diseased and control group. Cut-off to detect neuropathy for FA and ADC is 0.4835 and 1.1020 × 10 −3 mm2/s respectively. Conclusion: DTI though is challenging in peripheral nerves, however, is proving to be a powerful complementary tool for assessment of peripheral neuropathy. Our study validates its utility in infective neuropathies. Advances in knowledge: 1. DTI is a potential complementary tool for detection of peripheral neuropathies and can be incorporated in standard MR neurography protocol. 2. In leprosy-related ulnar neuropathy, altered signal intensity with thickening or abscess of the nerve is appreciated along with locoregional nodes and secondary denervation changes along with reduction of FA and rise in ADC value. 3. Best cut-offs obtained in our study for FA and ADC are 0.4835 and 1.1020 × 10 −3 mm2/s respectively.


2002 ◽  
Vol 282 (5) ◽  
pp. H1697-H1702 ◽  
Author(s):  
Hui Di Wang ◽  
Douglas G. Johns ◽  
Shanqin Xu ◽  
Richard A. Cohen

Our purpose was to address the role of NAPDH oxidase-derived superoxide anion in the vascular response to ANG II. Blood pressure, aortic superoxide anion, 3-nitrotyrosine, and medial cross-sectional area were compared in wild-type mice and in mice that overexpress human superoxide dismutase (hSOD). The pressor response to ANG II was significantly less in hSOD mice. Superoxide anion levels were increased twofold in ANG II-treated wild-type mice but not in hSOD mice. 3-Nitrotyrosine increased in aortic endothelium and adventitia in wild-type but not hSOD mice. In contrast, aortic medial cross-sectional area increased 50% with ANG II in hSOD mice, comparable to wild-type mice. The lower pressor response to ANG II in the mice expressing hSOD is consistent with a pressor role of superoxide anion in wild-type mice, most likely because it reacts with nitric oxide. Despite preventing the increase in superoxide anion and 3-nitrotyrosine, the aortic hypertrophic response to ANG II in vivo was unaffected by hSOD.


2018 ◽  
Vol 46 (5) ◽  
pp. 1214-1219 ◽  
Author(s):  
Sebastian A. Müller ◽  
Christopher H. Evans ◽  
Patricia E. Heisterbach ◽  
Martin Majewski

Background: The role of the paratenon in tendon healing is unknown. The present study compares healing in the presence or absence of the paratenon in an Achilles tendon defect model in rats. Hypothesis: Resection of the paratenon impairs tendon healing. Study Design: Controlled laboratory study. Methods: Sixty skeletally mature Sprague Dawley rats were randomly assigned to either a resected paratenon (RP) group or an intact paratenon (IP) group. In all animals, a 4-mm portion of the Achilles tendon was resected in the midsubstance. In the RP group, the paratenon was resected completely. In the IP group, the paratenon was opened longitudinally and closed again after the tendon defect had been created. One, 2, and 4 weeks after surgery, 7 animals per group were tested biomechanically and 3 animals per group examined histologically. Results: The recovery of mechanical strength was much more rapid in IP tendons. Tear resistance was significantly increased for IP tendons (41.3 ± 8.8 N and 47.3 ± 14.1 N, respectively) compared with RP tendons (19.3 ± 9.1 N and 33.2 ± 6.4 N, respectively) after 1 and 2 weeks. The cross-sectional area was larger in the IP group after 1 and 2 weeks (8.2 ± 2.3 mm2 and 11.3 ± 3.1 mm2 vs 5.0 ± 2.4 mm2 and 5.9 ± 2.0 mm2, respectively) compared with the RP group. Tendon stiffness was greater in the IP group after 1 week (10.4 ± 1.9 N/mm vs 4.5 ± 1.6 N/mm, respectively) compared with the RP group. In comparison, normal contralateral tendons had a maximal tear resistance of 56.6 ± 7.2 N, a cross-sectional area of 3.6 ± 0.7 mm2, and stiffness of 17.3 ± 3.8 N/mm. Hematoxylin and eosin staining revealed slightly delayed healing of RP tendons. Early collagen formation was seen in the IP group already after 1 week, whereas in the RP group, this only occurred after 2 weeks. After 4 weeks, the IP tendons showed more collagen crimp formation than the RP tendons. Conclusion: An intact paratenon promotes healing of the Achilles tendon. Clinical Relevance: Although incision or resection of the paratenon has been advocated when repairing injured or degenerative tendons, our data suggest that the integrity of the paratenon should be preserved.


2018 ◽  
Vol 6 (3) ◽  
pp. 301-308
Author(s):  
Sapna V. Amin ◽  
◽  
Deepika Pothakamuri ◽  
Prashant Adiga ◽  
Shripad Hebbar ◽  
...  

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Takahito Tamai ◽  
Tomokazu Murakawa ◽  
Osamu Yamaguchi ◽  
Shungo Hikoso ◽  
Issei Komuro ◽  
...  

Mammalian target of rapamycin (mTOR) is an evolutionary conserved Ser/Thr kinase and plays a key role in cellular growth. Multiprotein complexes called mTOR complex 1 (mTORC1) signaling is essential in cardiac hypertrophy. Many signaling pathways which can regulate mTORC1 activity have been previously reported, however, the regulation of mTORC1 is not fully elucidated. A small GTPase, Rheb (Ras homologue enriched in brain)-GTP activates mTORC1. In this study, to examine the contribution of Rheb in mTORC1 signaling in vivo hearts, we generated floxed Rheb mice to obtain cardiac-specific Rheb-deficient mice. First, to examine the role of Rheb-mTORC1 pathway in developmental cardiac hypertrophy, we generated Rheb-/- mice by crossing Rhebflox/flox mice with alpha MHC-Cre transgenic mice. Rheb-/- were born in Mendelian ratio. Echocardiographic analysis revealed that chamber dimension and contractile function of Rheb-/- were similar compared to those of control mice (Rheb+/+) 5 days after birth. However, all of them died between 8 and 10 days after birth due to cardiac dysfunction and heart failure. Rheb-/- exhibited cardiac dilatation and reduced contractility 8 days after birth. The heart weight to body weight ratio and the cross-sectional area of cardiomyocytes were significantly lower in Rheb-/- 8 days after birth. Next, to examine the role of Rheb-mTORC1 pathway in pathological hypertrophy, we generated conditional Rheb-/- mice by crossing Rhebflox/flox mice with Mer-Cre-Mer transgenic mice. Cardiac pressure overload was induced by means of transverse aortic constriction (TAC), and mice were sacrificed one week after TAC. The heart weight to tibia length ratio and the cross-sectional area of cardiomyocytes were significantly increased in both TAC-operated control and conditional Rheb-/- group compared to that of corresponding sham-operated group. Taken together, Rheb is not essential in pathological hypertrophy, but is essentilal in cardiac developmental hypertrophy in the post-neonatal period.


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