A functional artificial cell stabilized by a biomimetic cytoskeletons

 

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This is one of two research projects on bioengineering. KU Leuven is the home institution for this project. View the Melbourne-based partner project.

Applications for these projects are no longer being accepted

Cell-based products are being used with great impact in a wide diversity of both novel and long-established therapeutic applications. Erythrocytes, for example, are used to save thousands of lives every day worldwide. Yet, in low- and middle-income countries, their scarcity and unsafe control are endemic burdens that cost lives. Conversely, the high price tag of CAR-T cell products relegates such therapies to last-resort treatments even in developed countries. Therefore, synthetic strategies (i.e. artificial cells) could make such cell products safer and cheaper. In the paradigmatic case of Erythrocytes, the properties of their cytoskeleton are essential to establish and regulate blood flow, which in turn ensures adequate tissue oxygenation. These properties originate from their cortex, a “nanoscopic chassis” composed of multiple proteins that stabilize and anchors the cellular membrane above it. Attempts to reconstruct a similar cortex within giant unilamellar vesicles (GUVs) have so far delivered poor results with structures that cannot recover the properties of native Erythrocyte cortices.

In this project, we will adapt droplet-based microfluidic strategies for the formation of GUVs to integrate them with a “3D nano-printed” biomimetic cortex. Such structures will be obtained via 2-photon nano-lithographic techniques that have been demonstrated to offer the capacity to pattern nanometric scaffolds with dimensions similar to those of native cellular cortices. We will further characterize the physicochemical and functional properties of these cortex-stabilized GUVs in order to artificially recover specific properties (such as shape, deformability and gas exchange capacity) of native Erythrocytes.

Project goals

This project aims to achieve two main breakthroughs:

  1. Artificially construct a 3D cytoskeletal nano-structure that reproduces the shape, size and mechanical properties of the spectrin cortex of an Erythrocyte
  2. Integrate and anchor this artificial cortex within giant unilamellar vesicles (GUV) in order to build, from the bottom-up, an artificial cell that recovers several relevant characteristics of Erythrocytes:
    1. Biconcave shape;
    2. Mechanical properties; and
    3. Capacity for gas exchange.

To achieve these breakthroughs, we will deploy the following work plan:

  1. 3D nano-printed biomimetic cortex.
  2. Encapsulation of 3D cortices in GUVs.
  3. Physicochemical and functional characterization.

Supervision team

KU Leuven: Professor Xavier Casadevall i Solvas

The University of Melbourne: Dr David Collins

*Click on the researcher's name above to learn more about their publication and grant successes.

Who we are looking for

We are seeking a PhD candidate with the following skills:

  • Demonstrated experience in the field of biomedical engineering.
  • Demonstrated experience with biometrics.
  • Demonstrated ability to work independently and as part of a team.
  • Demonstrated time and project management skills.
  • Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
  • Excellent written and oral communication skills.
  • Demonstrated organisational skills, time management and ability to work to priorities.
  • Demonstrated problem-solving abilities.

Further details

The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.

Dr David Collins and Professor Xavier Casadevall i Solvas will lead the research teams in UoM and KUL, respectively. Professor Casadevall i Solvas will provide expertise in artificial cell generation (for both topics) and activities related to the integration of biomimetic scaffolds. Professor Bart Smeets and Professor Jeroen Lammertyn will provide expertise and support from the KUL side in terms of membrane protein integration and dynamics in artificial cells and microdevices/microfluidics. Dr Collins will provide expertise in micro/nanofabrication of biomimetic scaffolds, the development of acoustic microdevices, and numerical simulation. Associate Professor Daniel Scott and Professor Michael Parker will provide support from the UoM side in the form of expertise in mechanosensitive and pore-forming membrane proteins, respectively.

This PhD project will be based at KU Leuven with a minimum 12-month stay at the University of Melbourne.

The candidate will be enrolled in the PhD program at the Faculty of Bioscience Engineering/Biosystems at KU Leuven, and in the PhD program at the School of Chemical and Biomedical Engineering at the University of Melbourne.

Applications for these projects are no longer being accepted

First published on 1 February 2022.

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