Browsing by Author "Baker, Lane A."

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    Characterization of Membrane Patch-Ion Channel Probes for Scanning Ion Conductance Microscopy
    (Wiley, 2018-05) Shi, Wenqing; Zeng, Yuhan; Zhu, Cheng; Xiao, Yucheng; Cummins, Theodore R.; Hou, Jianghui; Baker, Lane A.; Biology, School of Science
    Integration of dual‐barrel membrane patch‐ion channel probes (MP‐ICPs) to scanning ion conductance microscopy (SICM) holds promise of providing a revolutionized approach of spatially resolved chemical sensing. A series of experiments are performed to further the understanding of the system and to answer some fundamental questions, in preparation for future developments of this approach. First, MP‐ICPs are constructed that contain different types of ion channels including transient receptor potential vanilloid 1 and large conductance Ca2+‐activated K+ channels to establish the generalizability of the methods. Next, the capability of the MP‐ICP platforms in single ion channel activity measurements is proved. In addition, the interplay between the SICM barrel and the ICP barrel is studied. For ion channels gated by uncharged ligands, channel activity at the ICP barrel is unaffected by the SICM barrel potential; whereas for ion channels that are gated by charged ligands, enhanced channel activity can be obtained by biasing the SICM barrel at potentials with opposite polarity to the charge of the ligand molecules. Finally, a proof‐of‐principle experiment is performed and site‐specific molecular/ionic flux sensing is demonstrated at single‐ion‐channel level, which show that the MP‐ICP platform can be used to quantify local molecular/ionic concentrations.
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    Electroceutical fabric lowers zeta potential and eradicates coronavirus infectivity upon contact
    (Nature, 2021-12) Ghatak, Subhadip; Khona, Dolly K.; Sen, Abhishek; Huang, Kaixiang; Jagdale, Gargi; Singh, Kanhaiya; Gopalakrishnan, Vinoj; Cornetta, Kenneth G.; Roy, Sashwati; Khanna, Savita; Baker, Lane A.; Sen, Chandan K.; Medical and Molecular Genetics, School of Medicine
    Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5 V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Porcine respiratory coronavirus AR310 particles (105) were placed in direct contact with the fabric for 1 or 5 min. Following one minute of contact, zeta potential of the porcine coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.
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    Ketoconazole Resistant Candida albicans is Sensitive to a Wireless Electroceutical Wound Care Dressing
    (Elsevier, 2021) Khona, Dolly K.; Roy, Sashwati; Ghatak, Subhadip; Huang, Kaixiang; Jagdale, Gargi; Baker, Lane A.; Sen, Chandan K.; Surgery, School of Medicine
    Wireless electroceutical dressing (WED) fabric kills bacteria and disrupts bacterial biofilm. This work tested, comparing with standard of care topical antibiotic ketoconazole, whether the weak electric field generated by WED is effective to manage infection caused by ketoconazole-resistant yeast Candida albicans. WED inhibited Candida albicans biofilm formation and planktonic growth. Unlike ketoconazole, WED inhibited yeast to hyphal transition and downregulated EAP1 curbing cell attachment. In response to WED-dependent down-regulation of biofilm-forming BRG1 and ROB1, BCR1 expression was markedly induced in what seems to be a futile compensatory response. WED induced NRG1 and TUP1, negative regulators of filamentation; it down-regulated EFG1, a positive regulator of hyphal pathway. Consistent with the anti-hyphal properties of WED, the expression of ALS3 and HWP1 were diminished. Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1 and EFG1. WED blunted efflux pump activity; this effect was in direct contrast to that of ketoconazole. WED exposure compromised cellular metabolism. In the presence of ketoconazole, the effect was synergistic. Unlike ketoconazole, WED caused membrane depolarization, changes in cell wall composition and loss of membrane integrity. This work presents first evidence that weak electric field is useful in managing pathogens which are otherwise known to be antibiotic resistant.