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Related Concept Videos

The Significance of Membrane Transport01:44

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
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Secondary Active Transport01:32

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One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
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The generation of electrical current in semiconductors is fundamentally driven by two mechanisms: drift and diffusion. These processes are essential for the functionality and performance of semiconductor-based devices.
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Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
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Mapping Molecular Diffusion in the Plasma Membrane by Multiple-Target Tracing MTT
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From Average Transient Transporter Currents to Microscopic Mechanism─A Bayesian Analysis.

August George1, Daniel M Zuckerman1

  • 1Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon 97239, United States.

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|February 19, 2024
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Summary
This summary is machine-generated.

Solid-supported membrane electrophysiology (SSME) can quantify kinetic parameters for secondary active transporters. Bayesian analysis of SSME data reveals practical identification of many parameters, guiding experimental design for complex models.

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Area of Science:

  • Structural Biology
  • Systems Biology
  • Biophysics

Background:

  • Electrophysiology has long provided mechanistic insights into secondary active transporters.
  • New experimental and analytical methods require evaluation for their capabilities and limitations.

Purpose of the Study:

  • To assess solid-supported membrane electrophysiology (SSME) for characterizing complex kinetic models (>10 rate constants).
  • To evaluate a Bayesian framework for parameter estimation, experimental design, and model selection using SSME data.

Main Methods:

  • Application of a Bayesian framework to synthetic SSME data.
  • Analysis of parameter precision under varying assumptions and incorporation of experimental uncertainties.
  • Comparison of Bayesian and maximum-likelihood approaches for model selection.

Main Results:

  • A subset of kinetic parameters can be practically identified within an order of magnitude using SSME data, even with measurement bias and input uncertainties.
  • Optimizing experimental conditions or combining experiments significantly increases the number of identifiable parameters.
  • The approach can distinguish between mechanisms and determine event order when not known in advance.

Conclusions:

  • SSME, analyzed within a Bayesian framework, is a powerful tool for elucidating transporter kinetics.
  • While some parameters remain challenging to estimate solely from SSME, optimized experiments enhance characterization.
  • The study provides guidance for robust Bayesian calculations in structural and systems biology.