12 Nov 2025
Precisely controlled photothermal forces redirect proteins towards bone formation.
A project at the Technical University of Munich (TUM) has successfully stimulated stem cells in a manner that reliably induced them to develop into bone cells.The technology could ultimately lead to ways to generate specific cells for biomedical applications, but is also a new step in the study of how exogenous forces can influence mammalian cell behavior, a complex and challenging topic.
Key cellular components and pathways are known to be involved in a cell's responses to outside forces, but investigations into these effects with micromanipulation techniques have suffered from a lack of resemblance to the natural microenvironment, commented TUM.
The project's solution was to design and create a new light-driven approach capable of applying spatially patterned exogenous forces to individual cells sat within multicellular clusters, and encased in 3D hydrogel matrices. The work was published in Advanced Materials.
The TUM lab of Berna Özkale Edelmann incorporated nanoscale gold rods and plastic chains into microgel cushions measuring 60 microns in size, together with a few human stem cells. When irradiated with 785-nanometer laser light, photothermal actuation created local contraction of the microgel network, through a combination of plasmonic heating and phase transition.
This in turn delivered mechanical forces to the stem cells, which responded accordingly. The technology gives the researchers significant control over the forces being created, as well as the temperatures and strains involved.
An unprecedented advance in the field
"We have developed a technology that allows forces to be applied to the cell very precisely in a three-dimensional environment,” said Özkale Edelmann. "This represents an unprecedented advance in the field."
The localized laser heating of the gel can precisely determine the forces with which the "nanorobots" press on a cell. In response biochemical processes are triggered, in which ion channels change their properties and proteins are activated, including one that is particularly important for bone formation or osteogenesis.
In trials TUM used mesenchymal stem cells, 10 to 20 microns in size and known to be able to differentiate into bone, cartilage and muscle cells. TUM found that its photothermal method could reliably trigger a stem cell to develop into a bone cell within three days, with the process completed within three weeks.
"Optical actuation provides excellent micron-scale resolution and millisecond responsiveness, generating tunable forces within a range of 17 to 34 nN, well suited for mechanotransduction studies," noted the TUM project in its paper.
The next steps will include automating the technology and scaling up the process, since any future clinical applications will require cell quantities numbered in the millions. TUM will also investigate whether the same laser stimulation can compel stem cells to become other forms of biomaterial besides bone.
"The corresponding stress pattern can also be found for cartilage and heart cells," said Özkale Edelman. "It's almost like at the gym: we train the cells for a particular area of application. Now we just have to find out which stress pattern suits each cell type."
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