Blebs are blister-like protrusions that occur at the cell surface (reviewed in [1]). Blebs form, and function, in a series of defined steps. They typically grow to around 2 µm in about 30 seconds before shrinking back for another 120 seconds. Blebs are well known as a by-product of apoptotic and necrotic processes, even though they are not essential for the execution of either of these programs [2]. In the past decades, the role that blebs play in locomotion of some cell types became increasingly acknowledged. For example, blebs-mediated cell motility was observed in early embryos and was termed amoeboid motility [3]. Blebbing (amoeboid motility) has been observed in studies of both unicellular [4, 5] and multicellular systems [6]. The unicellular form of Dictyostelium discoideum takes the form of an elliptical cell, which moves through alternating cycles of expansion and contraction, coupled with low-affinity substrate binding. These are both characteristic features of blebbing motility.

In multicellular eukaryotic systems, both leukocytes and certain tumor cells have been observed to move in an amoeboid fashion, distinct from that of mesenchymal migration [6]. These movements are generated by cortical actin and driven by weak and short-lived interactions with the substrate [7,8]. Some cancers preferentially use this type of motility to avoid the requirement for extracellular matrix (ECM) proteolysis [9] and escape tissue barriers [7].

Blebbing motility has also been observed in a variety of other cell types and model organisms, including fish embryonic cells [10, 3], primordial germ cells (PGCs) in zebrafish [11] and Drosophila melanogaster embryos [12].

Although blebbing is now known to be a mode of migration, much of the initial findings on the mechanics of blebbing comes from non-migratory cells. Subsequent studies suggest similar mechanisms are likely to be used by migratory cells. In both cases, the blebbing cycle can be simplified into 3 major steps, namely initiation, expansion and retraction [1].