Mineralization within macromolecular condensates – the chemical playground of living cells

Introduction

Organisms form crystalline materials with superior structural and mechanical properties. This arises from the ability of functional macromolecules to create intricate architectures via a multi-step crystallization process. Current approaches to engineer bioinspired minerals focus on interactions between macromolecules and minerals in dilute aqueous environments, rarely considering the emergent properties of macromolecular condensates.

Background

However, we and others showed that macromolecular crowding is intimately associated with biomineral formation in vivo. In this project, we will develop a new type of chemistry—dense-phase mineralization—to unlock the pathways mastered by nature.

Hypothesis

Our hypothesis is that weak polymer-ion interactions within dense phases tune the chemical landscape, controlling the crystallization process and the properties of its products. Remarkably, our preliminary results using the calcium carbonate system show that molar-range polymer concentrations, four orders of magnitude denser than in previous works, result in intricate crystals with life-like properties.

Methodology

We will investigate dense-phase mineralization in both synthetic and living systems, relying on our unique expertise in cryo-electron and X-ray microscopies of hydrated biological samples.

Aim 1

1. We will grow crystals in a dense polymer phase.
2. We will use the crowded environment to sculpt architectural motives.

Aim 2

1. We will investigate the challenging phase separation regime.
2. We will transform inorganic condensates into transient precursors for mineralization.

Aim 3

1. We will elucidate how liquid-liquid phase separation evolved by mineralizing organisms.
2. We will regulate inorganic condensate formation.

Conclusion

This project will open an uncharted chemical landscape to form and control bioinspired minerals. The outcome will be a toolbox for process design that allows us to optimize material properties—the highest gain we can ask for in bioinspired mineralization.