Polarization-sensitive stimulated Raman scattering imaging resolves amphotericin B orientation in Candida membrane

Ergosterol-targeting amphotericin B (AmB) is the first line of defense for life-threatening fungal infections. Two models have been proposed to illustrate AmB assembly in the cell membrane; one is the classical ion channel model in which AmB vertically forms transmembrane tunnel and the other is a recently proposed sterol sponge model where AmB is laterally adsorbed onto the membrane surface. To address this controversy, we use polarization-sensitive stimulated Raman scattering from fingerprint C═C stretching vibration to visualize AmB, ergosterol, and lipid in single fungal cells. Intracellular lipid droplet accumulation in response to AmB treatment is found. AmB is located in membrane and intracellular droplets. In the 16 strains studied, AmB residing inside cell membrane was highly ordered, and its orientation is primarily parallel to phospholipid acyl chains, supporting the ion channel model. Label-free imaging of AmB and chemical contents offers an analytical platform for developing low-toxicity, resistance-refractory antifungal agents.

A New Neuron Ion Channel Model with Noisy Input Current

The data processing fundamental problem affects all aspects of nervous-system function by the noise of ion channels. The conducting and non conducting of ion channels depends on random transitions of channel noise, which affect the states of several numbers of gates in every single individual ion channel. This paper, introduce a new ion channel model in the neuron with noisy input current as approximations of the HH model. It briefly introduces the ion channel based on stochastic Hodgkin-Huxley model. The method is able to fully constrain the HH model and obtain all models capable of reproducing the data. Therefore, this method overcomes the limitations of other parameter estimation methods. The stochastic Markov process method is simply applied to simulate each gate individually to determine the relationship between channel noise and the spike frequency.