# Molecular‐Scale Tuning of Low‐Molecular‐Weight Gelators Controls Supramolecular Assembly and Directs Human Mesenchymal Stem Cell Growth

## TL;DR

Changing a simple chemical group in a gelator alters how it self-assembles and affects how stem cells grow on it.

## Contribution

A minor molecular modification in a gelator leads to distinct supramolecular assemblies and stem cell growth behaviors.

## Key findings

- DBS-CH2OH forms a stiffer, organized hydrogel with different assembly properties compared to DBS-CONHNH2.
- hMSCs exhibit spread morphologies on DBS-CH2OH gels but rounded morphologies on DBS-CONHNH2 gels.
- Co-assembled gels combine properties of both LMWGs, influencing hMSC growth through structure and stiffness.

## Abstract

We report the synthesis and characterization of a simple alcohol‐functionalized low‐molecular‐weight gelator (LMWG) based on a 1,3:2,4‐dibenzylidenesorbitol scaffold (DBS‐CH2OH) and explore its self‐assembly in comparison to acylhydrazide‐functionalized DBS‐CONHNH2. DBS‐CH2OH forms a stiffer, highly organized, less‐soluble self‐assembled hydrogel, with a different assembly mode and much higher entropy/enthalpy of dissociation. On mixing, the LMWGs co‐assemble into gel nanofibers with similar thermodynamics to DBS‐CONHNH2. DBS‐CH2OH is an excellent scaffold for the growth of human mesenchymal stem cells (hMSCs), which exhibit extended spread‐shaped morphologies on the gel surface. In contrast, for DBS‐CONHNH2, hMSCs have a rounded morphology and penetrate into the softer gel. A simple functional group change on the LMWG, therefore, leads to a remarkable change in cell growth outcomes. When hMSCs are grown on the co‐assembled gel, they have the rounded morphology characteristic of DBS‐CONHNH2 but remain on the gel surface, like DBS‐CH2OH. The multi‐component gel thus shares characteristics of the individual LMWGs, with hMSC growth being controlled by factors like structure, stiffness, and dynamics. This work demonstrates how chemical manipulation of gels based on deceptively simple LMWGs can have profound impacts in biomaterials engineering.

Chemistry in charge of biology! Simple low‐molecular‐weight gelators, with minor modifications in molecular structure, self‐assemble differently and can also co‐assemble when simultaneously triggered. This creates a family of gels with different properties that direct the growth of stem cells in different ways.