Cells in tissue live in a complex mechanical environment that they have to sense and respond to. Mechanosensing has recently emerged as a key process underlying the functioning of the immune system, how stem cell acquires specific fates, and the healing of wounds. Yet, at a fundamental level, we don’t understand the molecular logic that cells use to mechanically sense their environment.
We study cell migration in both immune and cancer cells, systems where movement is central to function and pathology. Migration requires the seamless integration of many subroutines: cells must establish a front–back axis, decide where and when to move, and coordinate protrusions at the front and contractions at the rear. What are the rules of this self-organization? How do biochemical signals and mechanical forces collaborate to position polarity programs?
We explore the crosstalk between multiple currencies (signals, forces, and geometry) and how their misregulation drives disease progression, including cancer invasion and metastasis. Our approach is to pair biosensors to visualize a quantitative dynamic of choice inside living cells with precision tools (e.g., optogenetics) to control the regulators of these behaviors. We particularly focus on the molecular players allowing cells to spatially sense their environment and their downstream signaling effectors. By uncovering how cells interpret mechanical cues in space and time, we aim to define general principles of mechanosensing that transcend individual cell types, with broad implications for not only for cell migration but also cell fate decisions.
Cells rarely act alone. Multicellular coordination enables a dizzying array of cellular processes from the healing of our wounds to the beating of our hearts and the digestion of our meals. A striking example of this coordination is collective migration, in which cells move as cohesive units rather than as isolated individuals.
Collective migration underlies a wide spectrum of biological processes such as embryonic development and wound repair. In metastasis, tumor cells often leave the primary site as clusters rather than as single cells. Although less abundant, these clusters are strikingly potent, estimated to be 20 to 100 times more efficient at seeding metastases than solitary circulating tumor cells. The ability to polarize as a group appears to be a key determinant of their invasiveness, yet the mechanisms by which they form, polarize, and migrate remain poorly understood.
Our previous work has shown that mechanical signals transmitted within the membrane are essential for single migrating cell polarization and migration. We hypothesize that a similar mechanical–polarity program drives the behavior of cancer clusters. Using optogenetics, mechanical measurements, and migration assays in both cell lines and patient-derived samples, we aim to uncover the fundamental rules of cluster cohesion and invasion. More broadly, this research asks how cells leverage membrane mechanics to coordinate collective behaviors—principles that span from tissue repair to malignant spread and may reveal new vulnerabilities to halt metastasis at its roots.
Membrane tension is a fundamental physical property that shapes nearly every aspect of cell biology. It coordinates signaling, trafficking, migration, and polarity. To function, cells must keep membrane tension within a narrow optimal range, too high or too low, and essential processes falter. Yet, numerous internal and external factors can acutely alter membrane fluidity and tension. Just as a guitar string must be precisely tuned to play the right note, a cell’s membrane must maintain the right tension to coordinate movement, communication, and essential functions.
Cells therefore require robust mechanisms to sustain membrane homeostasis in the face of perturbations. This need is particularly evident in immune cells, whose polarity and motility depend on exquisitely tuned mechanics even as they navigate complex and shifting tissue environments. How cells sense and rapidly correct changes in membrane fluidity and tension, however, remains poorly understood.
We aim to uncover how cells preserve membrane homeostasis within complex tissues. We focus is on the tumor microenvironment, where metabolic gradients, poor vascularization, and chronic inflammation generate mechanically hostile niches. By examining how immune and tumor cells differentially adapt to these stresses, we seek to identify strategies to selectively reinforce membrane homeostasis, enhancing immune cell infiltration while constraining malignant invasion and spread.
