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European Biopharmaceutical Review

Scratching the Surface

The cell surface membrane – or plasma membrane (PM) – surrounds the cell providing the necessary boundaries between the cytoplasm and the extracellular environment. This thin, semi-permeable membrane plays a vital role in protecting the integrity of the cell through selective movement of substances passing in and out. It also constitutes the base for the attachment of cytoskeleton and cell walls – for bacteria and plants – thereby providing and maintaining the shape of the cell. Moreover, the PM allows cells to recognise one another and transmits signalling processes.

The building blocks of the cell membrane are lipids, proteins, and their associated sugars. The composition and relative concentration of these molecules define the membrane function and vary among different organisms, cell types, and cell states. Based on the fluid mosaic model introduced in 1972 by Singer and Nicolson, the PM is a mosaic of components – primarily phospholipids, cholesterol, proteins, and associated carbohydrates – moving freely and fluidly in the plane of the membrane. Although it was thought that the distribution of components is uniform, current data suggest that the cell membrane is highly and tightly organised in heterogeneous microdomains: the maintenance of this heterogeneity is associated with a large energetic cost indicating its significance (1). In support of this hypothesis, perturbations to the lipid composition of the membrane that disrupt the proposed compartmentalisation drastically reduce the efficiency of signal transduction (1).

Introducing the Surfaceome

Although lipids and glycans are key components of the PM, the focus of the present review is on the collection of proteins that resides at the cell surface or surfaceome. Surface proteins can be physically embedded in the lipid bilayer (integral), be anchored to the phospholipids or integral proteins at either side of the cell membrane (peripheral), or even associate to the membrane only under specific conditions. The surfaceome constitutes roughly 50% of the PM mass and exhibits a variety of functions that include transport, enzymatic activity, signal transduction, cell-cell interaction, and attachment to the cytoskeleton or the extracellular matrix (2). Different classes of surface proteins carry out these tasks for example channel and carrier proteins, enzymes, receptors, cell recognition, and cell adhesion proteins. Given the range of functions carried out by surface proteins, it is not surprising that roughly 30% of predicted open reading frames in a typical genome encode membrane and PM proteins (2).

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Dr Maria Pavlou studied biology at the University of Athens, Greece, and upon graduation moved to Canada to pursue her postgraduate studies. In January 2014, Maria obtained her PhD from the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Canada, under the supervision of Dr EP Diamandis, with a focus on the development of a novel proteomic prognostic signature for breast cancer patients. After her PhD, she joined the lab of Professor Dr Bernd Wollscheid at the Institute of Molecular Systems Biology at the Swiss Federal Institute of Technology, Zurich, as a post-doctoral fellow. Her research focused on understanding the signalling mechanisms employed by the foodborne pathogen Listeria monocytogenes to adapt and infect the human host. In September 2017, Maria joined Dualsystems Biotech as Senior Scientist where she is focusing on identifying targets and offtargets of orphan ligand on the surface of living cells using a chemoproteomic approach.

Dr Paul Helbling completed his Master’s degree in biology at the University of Zurich, Switzerland, and obtained his PhD in developmental biology at the Swiss Federal Institute of Technology (ETH) in Zurich. After his PhD, he worked at the Foundation for Cardiovascular Research and organised clinical studies according to Good Clinical Practice. Paul moved on to MDS Pharma Services where he held various positions in the Good Laboratory Practice (GLP)-compliant facilities, finally responsible for the ligand-binding group that specialised in the analysis of biologics and anti-drug antibodies. His next position was in business development at the Good Manufacturing Practicecompliant facilities of Solvias, responsible for southern Europe and Germany and opening new market territories in Turkey. Paul then became Head of Business Development at IBR, a GLPcompliant service provider specialising in cell-based assays. Finally, he joined the team at Dualsystems as CEO that is focusing on identifying targets and off-targets on the living cells using LC-MS/MS.
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Dr Maria Pavlou
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Dr Paul Helbling
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