In a groundbreaking study that may transform tissue engineering and cancer research, scientists at the Indian Institute of Technology Bombay (IIT-B) have demonstrated how cells can sense and respond to invisible mechanical patterns within their surroundings—reshaping the understanding of how cells align and organise in living tissue.
Led by Professor Abhijit Majumder, the research team investigated how cells behave in the presence of mechanical inhomogeneities—variations in stiffness—within soft materials. Their findings, published inCell Reports Physical Science, show that cells do not rely solely on chemical signals to orient themselves but also respond to minute, built-in mechanical strain fields.
“Mechanical inhomogeneities are quite common in living tissues, especially in tumours, healing wounds and developing organs. Yet we’re only beginning to understand how cells interpret these cues,” said Prof. Majumder.
To simulate such conditions, the researchers embedded a small glass bead into a soft hydrogel, replicating a rigid structure surrounded by a soft matrix—much like a tumour inside body tissue. When the gel swelled in water, the bead resisted the expansion, creating a pre-strain gradient, or a subtle stretch pattern. Upon introducing muscle precursor cells to this substrate, the researchers observed that the cells aligned radially around the bead, influenced by the invisible mechanical signals.
“These cells could detect and respond to the strain gradient created by the bead, aligning themselves in a radial pattern. The effect extended up to two millimetres from the bead—around 20 to 40 cell lengths,” explained lead author Dr Akshada Khadpekar. In contrast, on a uniform soft gel without the bead, the alignment was limited to just 0.35 millimetres.
The study ruled out chemical signalling as the cause of this alignment through rigorous control experiments involving different extracellular matrix proteins and varying gel stiffness. Only soft substrates produced the alignment effect, confirming its mechanical origin.
Collaborating with Professor Parag Tandaiya from IIT Bombay’s Department of Mechanical Engineering, the team used finite element simulations to model the strain fields in the gel. These simulations mirrored the patterns of alignment seen in experiments and were critical in validating the hypothesis.
The research extended beyond spherical beads to include hollow capillaries and other shapes, showing cells formed arcs, spirals and waves—adapting intelligently to the mechanical patterns. Furthermore, different types of cells were tested, and their alignment was found to depend on their force-generating capability and shape.
“This is the first time such a mechanically precise and intelligent cellular response has been documented in this way,” noted Prof. Tandaiya. The team developed a predictive model to determine how cells align based on their physical traits and substrate stiffness.
The implications are wide-ranging. In tissue engineering, this discovery could enable scientists to guide cell organisation simply by modifying material properties, avoiding complex scaffolding. In oncology, the stiffness of tumours may now be seen as an active participant in altering cellular environments. Similarly, in regenerative medicine, adjusting tissue mechanics might offer new strategies to restore healthy cell patterns.
“This opens up an entirely new perspective on how we can influence cellular behaviour, not with chemicals but with the silent language of mechanics,” Dr Khadpekar concluded.
