Understanding small molecule transport across cell membranes

Dr. Douglas Kell, University of Liverpool Research Chair in Systems Biology, investigates the transport of fluorescent small molecules across the plasma membrane. His work necessitates the often difficult rapid screening of up to 50 fluorophores at the same time. He discovered the solution through advanced flow cytometry.

Understanding small molecule transport across cell membranes

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Drug transport through the membrane

The plasma membrane is what isolates the cell’s interior from its surroundings. It is made up of a lipid bilayer and other macromolecules, such as carbohydrates, glycoproteins, and membrane proteins, which provide structure and restrict molecule transport across the cell.

The physical and chemical properties of a drug molecule determine its route into the cell. Most lipid-soluble drugs, for instance, can cross the membrane passively via the diffusion process. Other drugs enter the cell passively or actively by imitating the natural substrates of transporter proteins.

Scientists can reliably predict potential drug interactions, treatment efficacy, and resistance mechanisms if they know which transporter(s) a drug uses.

Dr Douglas Kell’s work on small molecule transport

Dr Kell’s lab is interested in small molecule transport across cellular membranes. His research is based on mammalian cell membrane transporters and bacterial transporters, several of which have yet to be identified. His group employs advanced flow cytometry to identify the uptake of small fluorescent molecules, which have previously had high structural similarity to several small molecule pharmaceuticals.

Recent research identified the molecular transporters responsible for psychoactive drug uptake into mammalian cells. They established competitive assays between the drugs of interest and their fluorophore mimics to answer this question. They utilized advanced flow cytometry to evaluate cell transport into mammalian cells by knocking out specific transporter proteins.

Why high throughput flow cytometry

The Kell lab uses the iQue® Advanced Flow Cytometry Platform for their research for several reasons:

  • Rapid analysis: The equipment is one of the fastest flow cytometers, helping them get more done in a day
  • High throughput: The iQue® can tackle 96 and 384 well plates, enabling the screening of numerous fluorescent small molecules at once
  • Versatility: It can identify small cells, so they can investigate the membrane biology of both mammalian cells and E.coli
  • Performance: The system provides sophisticated data, making it easy to identify intracellular fluorescence signals without interference from extracellular noise

Other projects in the lab include screening up to 50 fluorophores for transport into E. coli cells and using fluorophores to identify microbial cell proliferation after antibiotic treatment, with the goal of developing a rapid anti-microbial susceptibility test for urinary tract infections.

About Sartorius

Sartorius

Sartorius is a leading international pharmaceutical and laboratory equipment supplier. With our innovative products and services, we are helping our customers across the entire globe to implement their complex and quality-critical biomanufacturing and laboratory processes reliably and economically.

The Group companies are united under the roof of Sartorius AG, which is listed on the Frankfurt Stock Exchange and holds the majority stake in Sartorius Stedim Biotech S.A. Quoted on the Paris Stock Exchange, this subgroup is comprised mainly of the Bioprocess Solutions Division.

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A growing number of medications are biopharmaceuticals. These are produced using living cells in complex, lengthy and expensive procedures. The Bioprocess Solutions Division provides the essential products and technologies to accomplish this.

In fact, Sartorius has been pioneering and setting the standards for single-use products that are currently used throughout all biopharmaceutical manufacturing processes.

Making lab life easier

Lab work is complex and demanding: Despite repetitive analytical routines, lab staff must perform each step in a highly concentrated and careful way for accurate results.

The Lab Products and Services Division helps lab personnel excel because its products, such as laboratory balances, pipettes and lab consumables, minimize human error, simplify workflows and reduce physical workloads


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Last updated: Jun 9, 2023 at 7:36 AM

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