Project description
Synthetic transmembrane light-activated anion transporters
The transport of anions across the cell membrane is essential to many biological processes. The EU-funded LIGHTPORT research programme aims to develop a synthetic system with anion receptors in which the binding properties can be modulated by light and to use them as transmembrane carriers to regulate passive and induce active transport. The objectives of the programme include the development of visible-light-actuated photoswitches, the development of mechanically interlocked structures as photoswitchable hosts, the application of these structures for light-gated transport, and light-driven pumping of anions across phospholipid bilayers. The overarching goal is to use this work toward the development of light-based localised pharmacological treatment, such as light-triggered cancer or bacterial cell elimination.
Objective
The transport of anions across the cell membrane, which is mediated by transport proteins, is essential to many important biological processes. Dysregulation of this transport has been associated to various diseases and therefore, chemists endeavour to develop artificial receptors that mimic the function of natural transporters. Despite much progress over the last decade, the current artificial systems are mostly static, while proteins are able to change their activity dynamically in response to stimuli in the environment. To integrate such stimuli-controlled behavior in synthetic systems is a key contemporary challenge. In view of this, the goal of the proposed research program is to develop anion receptors in which the binding properties can be effectively modulated by light and to apply these receptors as transmembrane carriers and pumps, in order to regulate passive transport (i.e. down a concentration gradient) and to induce active transport (i.e. against a concentration gradient). This interdisciplinary program is divided into three work packages: WP1 aims at the development of structurally rigid and visible-light-actuated photoswitches and their use as platforms for constructing anion receptors; WP2 deals with the development of mechanically interlocked structures as photoswitchable anionic hosts; WP3 is directed at utilizing these receptors for light-gated transport and light-driven pumping of anions across phospholipid bilayers, whereas also an alternative dual-responsive anion channel will be prepared. Eventually, it is expected that this work will open a new route toward light-based localized pharmacological treatment, e.g. via light-triggered cancer or bacterial cell death. Furthermore, active transport systems, that are able to build up and maintain concentration gradients across membranes, could provide a completely new view on how to convert and store light (solar) energy.
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Funding Scheme
ERC-STG - Starting GrantHost institution
2311 EZ Leiden
Netherlands